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Shakerian N, Tafazoli A, Razavinia A, Sadrzadeh Aghajani Z, Bana N, Mard-Soltani M, Khalesi B, Hashemi ZS, Khalili S. Current Understanding of Therapeutic and Diagnostic Applications of Exosomes in Pancreatic Cancer. Pancreas 2025; 54:e255-e267. [PMID: 39661050 DOI: 10.1097/mpa.0000000000002414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
ABSTRACT Unusual symptoms, rapid progression, lack of reliable early diagnostic biomarkers, and lack of efficient treatment choices are the ongoing challenges of pancreatic cancer. Numerous research studies have demonstrated the correlation between exosomes and various aspects of pancreatic cancer. In light of these facts, exosomes possess the potential to play functional roles in the treatment, prognosis, and diagnosis of the pancreatic cancer. In the present study, we reviewed the most recent developments in approaches for exosome separation, modification, monitoring, and communication. Moreover, we discussed the clinical uses of exosomes as less invasive liquid biopsies and drug carriers and their contribution to the control of angiogenic activity of pancreatic cancer. Better investigation of exosome biology would help to effectively engineer therapeutic exosomes with certain nucleic acids, proteins, and even exogenous drugs as their cargo. Circulating exosomes have shown promise as reliable candidates for pancreatic cancer early diagnosis and monitoring in high-risk people without clinical cancer manifestation. Although we have tried to reflect the status of exosome applications in the treatment and detection of pancreatic cancer, it is evident that further studies and clinical trials are required before exosomes may be employed as a routine therapeutic and diagnostic tools for pancreatic cancer.
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Affiliation(s)
- Neda Shakerian
- From the Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful
| | - Aida Tafazoli
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz
| | - Amir Razavinia
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, IR
| | | | - Nikoo Bana
- Kish International Campus, University of Teheran
| | - Maysam Mard-Soltani
- From the Department of Clinical Biochemistry, Faculty of Medical Sciences, Dezful University of Medical Sciences, Dezful
| | - Bahman Khalesi
- Department of Research and Production of Poultry Viral Vaccine, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization, Karaj
| | - Zahra Sadat Hashemi
- ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran
| | - Saeed Khalili
- Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran
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2
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Liu M, Jiang H, Momeni MR. Epigenetic regulation of autophagy by non-coding RNAs and exosomal non-coding RNAs in colorectal cancer: A narrative review. Int J Biol Macromol 2024; 273:132732. [PMID: 38823748 DOI: 10.1016/j.ijbiomac.2024.132732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/16/2024] [Accepted: 05/19/2024] [Indexed: 06/03/2024]
Abstract
One of the major diseases affecting people globally is colorectal cancer (CRC), which is primarily caused by a lack of effective medical treatment and a limited understanding of its underlying mechanisms. Cellular autophagy functions to break down and eliminate superfluous proteins and substances, thereby facilitating the continual replacement of cellular elements and generating vital energy for cell processes. Non-coding RNAs and exosomal ncRNAs have a crucial impact on regulating gene expression and essential cellular functions such as autophagy, metastasis, and treatment resistance. The latest research has indicated that specific ncRNAs and exosomal ncRNA to influence the process of autophagy in CRC cells, which could have significant consequences for the advancement and treatment of this disease. It has been determined that a variety of ncRNAs have a vital function in regulating the genes essential for the formation and maturation of autophagosomes. Furthermore, it has been confirmed that ncRNAs have a considerable influence on the signaling pathways associated with autophagy, such as those involving AMPK, AKT, and mTOR. Additionally, numerous ncRNAs have the potential to affect specific genes involved in autophagy. This study delves into the control mechanisms of ncRNAs and exosomal ncRNAs and examines how they simultaneously influence autophagy in CRC.
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Affiliation(s)
- Minghua Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China
| | - Hongfang Jiang
- Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China.
| | - Mohammad Reza Momeni
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
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3
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Zhang Y, Huo M, Li W, Zhang H, Liu Q, Jiang J, Fu Y, Huang C. Exosomes in tumor-stroma crosstalk: Shaping the immune microenvironment in colorectal cancer. FASEB J 2024; 38:e23548. [PMID: 38491832 DOI: 10.1096/fj.202302297r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 01/26/2024] [Accepted: 02/26/2024] [Indexed: 03/18/2024]
Abstract
Colorectal cancer (CRC) is a multifaceted disease characterized by a complex interaction between tumor cells and the surrounding microenvironment. Within this intricate landscape, exosomes have emerged as pivotal players in the tumor-stroma crosstalk, influencing the immune microenvironment of CRC. These nano-sized vesicles, secreted by both tumoral and stromal cells, serve as molecular transporters, delivering a heterogeneous mix of biomolecules such as RNAs, proteins, and lipids. In the CRC context, exosomes exert dual roles: they promote tumor growth, metastasis, and immune escape by altering immune cell functions and activating oncogenic signaling pathways and offer potential as biomarkers for early CRC detection and treatment targets. This review delves into the multifunctional roles of exosomes in the CRC immune microenvironment, highlighting their potential implications for future therapeutic strategies and clinical outcomes.
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Affiliation(s)
- Yawei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Mingyu Huo
- Department of Gastrointestinal Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Wenchao Li
- Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hongyu Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Qi Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jianwu Jiang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yang Fu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Changjun Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Chak PT, Kam NW, Choi TH, Dai W, Kwong DLW. Unfolding the Complexity of Exosome-Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma. Cancers (Basel) 2024; 16:919. [PMID: 38473281 DOI: 10.3390/cancers16050919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 02/19/2024] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open
Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy situated in the posterolateral nasopharynx. NPC poses grave concerns in Southeast Asia due to its late diagnosis. Together with resistance to standard treatment combining chemo- and radiotherapy, NPC presents high metastatic rates and common recurrence. Despite advancements in immune-checkpoint inhibitors (ICIs) and cytotoxic-T-lymphocytes (CTLs)-based cellular therapy, the exhaustive T cell profile and other signs of immunosuppression within the NPC tumour microenvironment (TME) remain as concerns to immunotherapy response. Exosomes, extracellular vesicles of 30-150 nm in diameter, are increasingly studied and linked to tumourigenesis in oncology. These bilipid-membrane-bound vesicles are packaged with a variety of signalling molecules, mediating cell-cell communications. Within the TME, exosomes can originate from tumour, immune, or stromal cells. Although there are studies on tumour-derived exosomes (TEX) in NPC and their effects on tumour processes like angiogenesis, metastasis, therapeutic resistance, there is a lack of research on their involvement in immune evasion. In this review, we aim to enhance the comprehension of how NPC TEX contribute to cellular immunosuppression. Furthermore, considering the detectability of TEX in bodily fluids, we will also discuss the potential development of TEX-related biomarkers for liquid biopsy in NPC as this could facilitate early diagnosis and prognostication of the disease.
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Affiliation(s)
- Paak-Ting Chak
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
| | - Ngar-Woon Kam
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
- Laboratory for Synthetic Chemistry and Chemical Biology Limited, Hong Kong Science Park, New Territories, Hong Kong 999077, China
| | - Tsz-Ho Choi
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
| | - Wei Dai
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
- Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
| | - Dora Lai-Wan Kwong
- Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
- Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
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The Role of Exosomes in Pancreatic Ductal Adenocarcinoma Progression and Their Potential as Biomarkers. Cancers (Basel) 2023; 15:cancers15061776. [PMID: 36980662 PMCID: PMC10046651 DOI: 10.3390/cancers15061776] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/05/2023] [Accepted: 03/08/2023] [Indexed: 03/17/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful. Exosomes, small extracellular vesicles (sEVs), are cell-secreted entities with diameters ranging from 50 to 150 nm that deliver cellular contents (e.g., proteins, lipids, and nucleic acids) from parent cells to regulate the cellular processes of targeted cells. Recently, an increasing number of studies have reported that exosomes serve as messengers to facilitate stromal-immune crosstalk within the PDAC tumor microenvironment (TME), and their contents are indicative of disease progression. Moreover, evidence suggests that exosomes with specific surface markers are capable of distinguishing patients with PDAC from healthy individuals. Detectable exosomes in bodily fluids (e.g., blood, urine, saliva, and pancreatic juice) are omnipresent and may serve as promising biomarkers for improving early detection and evaluating patient prognosis. In this review, we shed light on the involvement of exosomes and their cargos in processes related to disease progression, including chemoresistance, angiogenesis, invasion, metastasis, and immunomodulation, and their potential as prognostic markers. Furthermore, we highlight feasible clinical applications and the limitations of exosomes in liquid biopsies as tools for early diagnosis as well as disease monitoring. Taking advantage of exosomes to improve diagnostic capacity may provide hope for PDAC patients, although further investigation is urgently needed.
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Li C, Qin T, Jin Y, Hu J, Yuan F, Cao Y, Duan C. Cerebrospinal fluid-derived extracellular vesicles after spinal cord injury promote vascular regeneration via PI3K/AKT signaling pathway. J Orthop Translat 2023; 39:124-134. [PMID: 36909861 PMCID: PMC9999163 DOI: 10.1016/j.jot.2023.02.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 02/02/2023] [Accepted: 02/06/2023] [Indexed: 03/14/2023] Open
Abstract
Background The cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, is predominantly produced by the choroid plexus of the ventricle. Although CSF-derived extracellular vesicles (CSF-EVs) may be utilized as diagnostic and prognostic indicators for illnesses of the central nervous system (CNS), it is uncertain if CSF-EVs may have an impact on neurological function after spinal cord injury (SCI). Methods Here, we isolated EVs using ultracentrifugation after extracting CSF from Bama miniature pigs. We then combined CSF-EVs with hydrogel and put it on the spinal cord's surface. To determine if CSF-EVs had an impact on mice's neurofunctional recovery, behavioral evaluations were employed. Both in vitro and in vivo, the effect of CSF-EVs on angiogenesis was assessed. We investigated whether CSF-EVs stimulated the PI3K/AKT pathway to alter angiogenesis using the PI3K inhibitor LY294002. Results CSF-EVs were successfully isolated and identified by transmission electron microscope (TEM), nano-tracking analysis (NTA), and western blot. CSF-EVs could be ingested by vascular endothelial cells as proved by in vivo imaging and immunofluorescence. We demonstrated that CSF-EVs derived from pigs with SCI (SCI-EVs) showed a better effect on promoting vascular regeneration as compared to CSF-EVs isolated from pigs receiving laminectomy (Sham-EVs). Behavioral assessments demonstrated that SCI-EVs could dramatically enhance motor and sensory function in mice with SCI. Western blot analysis suggested that SCI-EVs promote angiogenesis by activating PI3K/AKT signaling pathway, and the pro-angiogenetic effect of SCI-EVs was attenuated by the application of the LY294002 (PI3K inhibitor). Conclusion Our study revealed that CSF-EVs could enhance vascular regeneration by activating the PI3K/AKT pathway, hence improving motor function recovery after SCI, which may offer potential novel therapeutic options for acute SCI. The translational potential of this article This study demonstrated the promotion of vascular regeneration and neurological function of CSF-derived exosomes, which may provide a potential therapeutic approach for the treatment of spinal cord injury.
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Affiliation(s)
- Chengjun Li
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
| | - Tian Qin
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
| | - Yuxin Jin
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
| | - Jianzhong Hu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
| | - Feifei Yuan
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
| | - Yong Cao
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
| | - Chunyue Duan
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Road 87, Changsha, 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China
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7
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Wang Y, Wang S, Li L, Zou Y, Liu B, Fang X. Microfluidics‐based molecular profiling of tumor‐derived exosomes for liquid biopsy. VIEW 2023. [DOI: 10.1002/viw.20220048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Affiliation(s)
- Yuqing Wang
- School of Pharmacy Shanghai Stomatological Hospital Department of Chemistry Fudan University Shanghai China
| | - Shurong Wang
- School of Pharmacy Shanghai Stomatological Hospital Department of Chemistry Fudan University Shanghai China
| | - Lanting Li
- School of Pharmacy Shanghai Stomatological Hospital Department of Chemistry Fudan University Shanghai China
| | - Yan Zou
- School of Pharmacy Shanghai Stomatological Hospital Department of Chemistry Fudan University Shanghai China
| | - Baohong Liu
- School of Pharmacy Shanghai Stomatological Hospital Department of Chemistry Fudan University Shanghai China
| | - Xiaoni Fang
- School of Pharmacy Shanghai Stomatological Hospital Department of Chemistry Fudan University Shanghai China
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8
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Tung D, McKay BS. Decoding Race and Age-Related Macular Degeneration: GPR 143 Activity Is the Key. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1415:43-47. [PMID: 37440012 DOI: 10.1007/978-3-031-27681-1_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the developed world. Caucasians are eightfold more likely to develop AMD than any other race, indicating a racial bias in AMD incidence which is unexplained. We hypothesize that pigmentation of the retinal pigment epithelium (RPE) and choroid protects from AMD and underlies this peculiar racial bias. We investigated GPR143, a receptor in the pigmentation pathway, which is activated by a melanin synthesis by-product, l-dopa. In this model, greater pigmentation leads to greater l-dopa production and, in turn, greater GPR143 signaling. GPR143 activity upregulates PEDF and downregulates both VEGF and exosomes; all of which reduce the angiogenic potential in the retina. Moreover, we demonstrate that GPR143 signaling enhances the digestion of shed photoreceptor outer segments. Together, our data suggests a central role for GPR143 signaling in RPE-photoreceptor interaction which is critical to healthy vision.
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Affiliation(s)
- Dorothy Tung
- Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA
| | - Brian S McKay
- Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA.
- Department of Physiology, University of Arizona, Tucson, AZ, USA.
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9
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Ren J, Liu R. The Implication of Liquid Biopsy in the Non-small Cell Lung Cancer: Potential and Expectation. Methods Mol Biol 2023; 2695:145-163. [PMID: 37450117 DOI: 10.1007/978-1-0716-3346-5_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
Nowadays, lung cancer has remained the most lethal cancer, despite great advances in diagnosis and treatment. However, a large proportion of patients were diagnosed with locally advanced or metastatic disease and have poor prognosis. Immunotherapy and targeted drugs have greatly improved the survival and prognosis of patients with advanced lung cancer. However, how to identify the optimal patients to accept those therapies and how to monitor therapeutic efficacy are still in dispute. In the past few decades, tissue biopsy, including percutaneous fine needle biopsy and surgical excision, has still been the gold standard for examining the gene mutation such as EGFR, ALK, ROS, and PD-1/PD/L1, which can indicate the follow-up treatment. Nevertheless, the biopsy techniques mentioned above were invasive and unrepeatable, which were not suitable for advanced patients. Liquid biopsy, accounting for heterogeneity compared with tissue biopsy, is an alternative technique for monitoring the mutation, and a large quantity of research has demonstrated its feasibility to detect the circulating tumor cell, cell-free DNA, circulating tumor DNA, and extracellular vesicles from peripheral venous blood. The proposal of the concept of precision medicine brings a novel medical model developed with the rapid progress of genome sequencing technology and the cross-application of bioinformation, which was based on personalized medicine. The emerging method of liquid biopsy might contribute to promoting the development of precision medicine. In this review, we intend to describe the liquid biopsy in non-small cell lung cancer in detail in the aspect of screening, diagnosis, monitoring, treatment, and drug resistance.
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Affiliation(s)
- Jianghao Ren
- Shanghai Lung Tumor Clinical Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China
| | - Ruijun Liu
- Shanghai Lung Tumor Clinical Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R. China
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10
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Yunusova N, Dzhugashvili E, Yalovaya A, Kolomiets L, Shefer A, Grigor’eva A, Tupikin A, Kondakova I, Tamkovich S. Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients. Int J Mol Sci 2022; 24:ijms24010464. [PMID: 36613908 PMCID: PMC9820379 DOI: 10.3390/ijms24010464] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/09/2022] [Accepted: 12/19/2022] [Indexed: 12/29/2022] Open
Abstract
Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.
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Affiliation(s)
- Natalia Yunusova
- Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
- Department of Biochemistry and Molecular Biology, Faculty of Medicine and Biology, Siberian State Medical University, 634050 Tomsk, Russia
| | - Ekaterina Dzhugashvili
- V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia
| | - Alena Yalovaya
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
| | - Larisa Kolomiets
- Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Aleksei Shefer
- V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
| | - Alina Grigor’eva
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
| | - Alexey Tupikin
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
| | - Irina Kondakova
- Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Svetlana Tamkovich
- V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
- Correspondence:
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11
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He B, Huang Z, Huang C, Nice EC. Clinical applications of plasma proteomics and peptidomics: Towards precision medicine. Proteomics Clin Appl 2022; 16:e2100097. [PMID: 35490333 DOI: 10.1002/prca.202100097] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/16/2022] [Accepted: 04/28/2022] [Indexed: 02/05/2023]
Abstract
In the context of precision medicine, disease treatment requires individualized strategies based on the underlying molecular characteristics to overcome therapeutic challenges posed by heterogeneity. For this purpose, it is essential to develop new biomarkers to diagnose, stratify, or possibly prevent diseases. Plasma is an available source of biomarkers that greatly reflects the physiological and pathological conditions of the body. An increasing number of studies are focusing on proteins and peptides, including many involving the Human Proteome Project (HPP) of the Human Proteome Organization (HUPO), and proteomics and peptidomics techniques are emerging as critical tools for developing novel precision medicine preventative measures. Excitingly, the emerging plasma proteomics and peptidomics toolbox exhibits a huge potential for studying pathogenesis of diseases (e.g., COVID-19 and cancer), identifying valuable biomarkers and improving clinical management. However, the enormous complexity and wide dynamic range of plasma proteins makes plasma proteome profiling challenging. Herein, we summarize the recent advances in plasma proteomics and peptidomics with a focus on their emerging roles in COVID-19 and cancer research, aiming to emphasize the significance of plasma proteomics and peptidomics in clinical applications and precision medicine.
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Affiliation(s)
- Bo He
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, P. R. China
| | - Zhao Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, P. R. China
| | - Canhua Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, P. R. China.,Department of Pharmacology, and Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang, China
| | - Edouard C Nice
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
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12
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Liu SF, Li LY, Zhuang JL, Li MM, Ye LC, Chen XR, Lin S, Chen CN. Update on the application of mesenchymal stem cell-derived exosomes in the treatment of Parkinson's disease: A systematic review. Front Neurol 2022; 13:950715. [PMID: 36262830 PMCID: PMC9573985 DOI: 10.3389/fneur.2022.950715] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/07/2022] [Indexed: 11/30/2022] Open
Abstract
Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.
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Affiliation(s)
- Shu-fen Liu
- Department of Neurology, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University, Quanzhou, China
| | - Lin-yi Li
- Department of Neurology, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University, Quanzhou, China
| | - Jian-long Zhuang
- Prenatal Diagnosis Center, Quanzhou Women's and Children's Hospital, Quanzhou, China
| | - Mi-mi Li
- Department of Neurology, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University, Quanzhou, China
| | - Li-chao Ye
- Department of Neurology, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University, Quanzhou, China
| | - Xiang-rong Chen
- Department of Neurosurgery, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University, Quanzhou, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- Shu Lin
| | - Chun-nuan Chen
- Department of Neurology, The Second Affiliated Hospital, The Second Clinical Medical College, Fujian Medical University, Quanzhou, China
- *Correspondence: Chun-nuan Chen
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[Research Advances of Immunotherapy of Exosome PD-L1
in Non-small Cell Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2022; 25:689-695. [PMID: 36172735 PMCID: PMC9549428 DOI: 10.3779/j.issn.1009-3419.2022.102.33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cancer immunotherapy is increasingly popular in the field of cancer treatment, and related research is emerging. For patients with non-small cell lung cancer (NSCLC), in recent years, immune checkpoint inhibitors (ICIs) represented by programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunosuppressants, have become one of the most promising treatments for malignant tumors. Immune checkpoint blockade therapy includes anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) mAb, anti-PD-1 mAb and anti-PD-L1 mAb, with the best-known number of PD-L1 immunotherapy. At present, ICIs have achieved very good therapeutic results in clinical treatment, but with less effective efficiency, so we hope to obtain higher therapeutic efficiency. In recent years, exosomal PD-L1 has played an important role in the progress of immunotherapy for NSCLC. This paper reviews the effects of tumor exosomal PD-L1 protein on the tumor microenvironment, the effect prediction of immunotherapy, and as novel therapeutic strategies for immunotherapy in NSCLC.
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The Neuroprotection Effects of Exosome in Central Nervous System Injuries: a New Target for Therapeutic Intervention. Mol Neurobiol 2022; 59:7152-7169. [DOI: 10.1007/s12035-022-03028-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 09/05/2022] [Indexed: 11/25/2022]
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Li R, Zhou J, Wu X, Li H, Pu Y, Liu N, Han Z, Zhou L, Wang Y, Zhu H, Yang L, Li Q, Ji Q. Jianpi Jiedu Recipe inhibits colorectal cancer liver metastasis via regulating ITGBL1-rich extracellular vesicles mediated activation of cancer-associated fibroblasts. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 100:154082. [PMID: 35381565 DOI: 10.1016/j.phymed.2022.154082] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 01/05/2022] [Accepted: 03/26/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Extracellular vesicles (EVs) contribute greatly to the formation of pre-metastatic niche and tumor metastasis. Our previous study has revealed that tumor-derived ITGBL1 (integrin beta- like 1)-rich EVs activate fibroblasts through the NF-κB signaling to promote colorectal cancer (CRC) metastasis. Targeting ITGBL1-loaded EVs may be a new and effective therapy for treating CRC metastasis. Simultaneously, our preliminary clinical trial has demonstrated that Jianpi Jiedu Recipe (JPJDR) was an ideal alternative traditional Chinese medicine for the prevention and treatment of CRC metastasis. However, the underlying mechanism of JPJDR in the prevention of CRC metastasis is not clear. In this study, we will investigate the regulatory effect of JPJDR on ITGBL1 levels in CRC-derived EVs, and to detect how JPJDR regulate ITGBL1-rich EVs mediated activation of fibroblasts to inhibit CRC metastasis. METHODS EVs derived from CRC cells with/without JPJDR treatment were obtained by ultracentrifugation, following by characterization with electron microscopy, LM10 nanoparticle characterization system and western blot. The migration and growth of CRC cells were tested by transwell assay, wound healing assay and colony formation assay. The effect of JPJDR on the fibroblasts-activation associated inflammatory factors including IL-6, IL-8 and α-SMA was detected by real-time PCR. The levels of IL-6, IL-8 and α-SMA in the cell culture supernatant were detected by ELISA. The protein expressions of TNFAIP3, ITGBL1, p-NF-κB, IκBα and β-actin were detected by western blot. Liver metastasis model in mice was established by injecting MC38 single cell suspension into the spleen of mice to observe the effect of JPJDR on CRC liver metastasis. Immunohistochemistry were applied to detect the expression of ITGBL1 and TNFAIP3 in the liver metastatic tissues. Tissue immunofluorescence detection was performed to observe the regulatory effect of JPJDR on the ITGBL1-NF-κB signaling pathway. Cancer-associated fibroblasts (CAFs) in the liver metastatic tissues were sorted and characterized by platelet-derived growth factor receptor β (PDGFRβ) with flow cytometry, following by the detection of inflammatory factors including IL-6, IL-8 and α-SMA using real-time PCR. RESULTS JPJDR reduced the ITGBL1 levels in CRC cells-derived EVs. JPJDR inhibited the migration and growth of CRC cells via regulating ITGBL1-rich EVs mediated fibroblasts activity. Mechanically, JPJDR decreased fibroblasts activation by regulating ITGBL1-rich EVs mediated TNFAIP3-NF-κB signaling. Further in vivo experiments demonstrated that JPJDR reduced CRC liver metastasis by regulating ITGBL1-rich EVs secretion from CRC and blocked the fibroblasts activation by regulating ITGBL1-TNFAIP3- NF-κB signaling. CONCLUSION Our research demonstrated that JPJDR preventd CRC liver metastasis via down-regulating CRC-derived ITGBL1-loaded EVs mediated activation of CAFs, providing the experimental evidence for the clinical application of JPJDR in the prevention and treatment of CRC metastasis. More importantly, our study confirmed the great benefits of therapeutic targeting the EVs-mediated metastasis and warranted future clinical validation.
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Affiliation(s)
- Ruixiao Li
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jing Zhou
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinnan Wu
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haoze Li
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yunzhou Pu
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ningning Liu
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhifen Han
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lihong Zhou
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Wang
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Huirong Zhu
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Liu Yang
- Department of Oncology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Qi Li
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Qing Ji
- Department of Medical Oncology & Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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He Q, Liu L, Wei J, Jiang J, Rong Z, Chen X, Zhao J, Jiang K. Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review. Cell Death Dis 2022; 8:158. [PMID: 35379788 PMCID: PMC8979943 DOI: 10.1038/s41420-022-00962-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 12/13/2022]
Abstract
Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research.
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Affiliation(s)
- Qijin He
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Limin Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Jingge Wei
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Jiaying Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Zheng Rong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, No. 154 Anshan Road, Tianjin, 300052, China.
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Grimaldi AM, Salvatore M, Cavaliere C. Diagnostic and prognostic significance of extracellular vesicles in prostate cancer drug resistance: A systematic review of the literature. Prostate Cancer Prostatic Dis 2022:10.1038/s41391-022-00521-w. [PMID: 35264776 DOI: 10.1038/s41391-022-00521-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/04/2022] [Accepted: 02/16/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy. However, a fraction of men relapse after initial treatment because they develop drug resistance. The failure of anticancer drugs leaves resistant cancer cells to survive and proliferate, negatively affecting patient survival. Thus, drug resistance remains a significant obstacle to the effective treatment of prostate cancer patients. In this scenario, the involvement of extracellular vesicles (EVs) in intrinsic and acquired resistance have been reported in several tumors, and accumulating data suggests that their differential content can be used as diagnostic or prognostic factors. Thus, we propose a systematic study of literature to provide a snapshot of the current scenario regarding EVs as diagnostic and prognostic biomarkers resource in resistant prostate cancer. METHODS We performed the current systematic review according to PRISMA guidelines and comprehensively explored PubMed, EMBASE and Google Scholar databases to achieve the article search. RESULTS Thirty-three studies were included and investigated. Among all systematically reviewed EV biomarkers, we found mainly molecules with prognostic significance (61%), molecules with diagnostic relevance (18%), and molecules that serve both purposes (21%). Moreover, among all analyzed molecules isolated from EVs, proteins, mRNAs, and miRNAs emerged to be the most investigated and proposed as potential tools to diagnose or predict resistance/sensitivity to advanced PCa treatments. DISCUSSION Our analysis provides a snapshot of the current scenario regarding EVs as potential clinical biomarkers in resistant PCa. Nevertheless, despite many efforts, the use of EV biomarkers in PCa is currently at an early stage: none of the selected EV biomarkers goes beyond preclinical studies, and their translatability is yet far from clinical settings.
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Li P, Lu X, Hu J, Dai M, Yan J, Tan H, Yu P, Chen X, Zhang C. Human amniotic fluid derived-exosomes alleviate hypoxic encephalopathy by enhancing angiogenesis in neonatal mice after hypoxia. Neurosci Lett 2022; 768:136361. [PMID: 34826550 DOI: 10.1016/j.neulet.2021.136361] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 11/11/2021] [Accepted: 11/19/2021] [Indexed: 12/17/2022]
Abstract
Neonatal hypoxic encephalopathy is a type of central nervous system dysfunction manifested by high mortality and morbidity. Exosomes play a crucial role in neuroprotection by enhancing angiogenesis. The objective of this study was to investigate the effect of human amniotic fluid-derived exosomes (hAFEXOs) on functional recovery in neonatal hypoxic encephalopathy. The transwell assay, scratch wound healing assay, and tube formation assay were used to evaluate the effect of hAFEXOs on the angiogenesis of human umbilical vein endothelial cells (HUVECs) after oxygen and glucose deprivation (OGD). The angiogenesis of microvascular endothelial cells (MECs) in the cortex was tested in neonatal mice treated with hAFEXOs or phosphate-buffered saline (PBS) after hypoxia. Expressions of hypoxia-inducible factor 1 α (HIF-1α) and vascular endothelial growth factor (VEGF) in the cerebral cortex were also tested by western blot. The Morris Water Maze Test (MWM) was carried out to detect the performance of spatial memory after processing with hAFEXOs or PBS. The results indicated that hAFEXOs favored tubing formation and migration of HUVECs after in vitro OGD. The hAFEXOs also favored the expression of CD31 in neonatal mice following hypoxia. The expressions of both HIF-1α and VEGF were significantly augmented in the cerebral cortex of neonatal mice which were treated with hAFEXOs. Moreover, the MWM test results showed that the performance of the spatial memory was better in the hAFEXO-treated group than in the PBS-treated group. Our study indicates that hAFEXOs alleviated hypoxic encephalopathy and enhanced angiogenesis in neonatal mice after hypoxia. In addition, hAFEXOs promoted migration and tube formation of HUVECs after OGD in vitro. These findings confirm that hAFEXOs show great potential for further studies aimed at developing therapeutic agents for hypoxic encephalopathy.
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Affiliation(s)
- Ping Li
- Department of Obstetrics, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha 410008, China
| | - Xiaoxu Lu
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jiajia Hu
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Minhui Dai
- Department of Clinical Dietitian, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jianqin Yan
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Huiling Tan
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China
| | - Peilin Yu
- School of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xuliang Chen
- Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
| | - Chengliang Zhang
- Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
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Kang SY, Lee EJ, Byun JW, Han D, Choi Y, Hwang DW, Lee DS. Extracellular Vesicles Induce an Aggressive Phenotype in Luminal Breast Cancer Cells Via PKM2 Phosphorylation. Front Oncol 2021; 11:785450. [PMID: 34966685 PMCID: PMC8710663 DOI: 10.3389/fonc.2021.785450] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 11/24/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Aerobic glycolysis is a hallmark of glucose metabolism in cancer. Previous studies have suggested that cancer cell-derived extracellular vesicles (EVs) can modulate glucose metabolism in adjacent cells and promote disease progression. We hypothesized that EVs originating from cancer cells can modulate glucose metabolism in recipient cancer cells to induce cell proliferation and an aggressive cancer phenotype. METHODS Two breast cancer cell lines with different levels of glycolytic activity, MDA-MB-231 cells of the claudin-low subtype and MCF7 cells of the luminal type, were selected and cocultured as the originating and recipient cells, respectively, using an indirect coculture system, such as a Transwell system or a microfluidic system. The [18F]fluorodeoxyglucose (FDG) uptake by the recipient MCF7 cells was assessed before and after coculture with MDA-MB-231 cells. Proteomic and transcriptomic analyses were performed to investigate the changes in gene expression patterns in the recipient MCF7 cells and MDA-MB-231 cell-derived EVs. RESULTS FDG uptake by the recipient MCF7 cells significantly increased after coculture with MDA-MB-231 cells. In addition, phosphorylation of PKM2 at tyrosine-105 and serine-37, which is necessary for tumorigenesis and aerobic glycolysis, was highly activated in cocultured MCF7 cells. Proteomic profiling revealed the proliferation and dedifferentiation of MCF7 cells following coculture with MDA-MB-231 cells. Transcriptomic analysis demonstrated an increase in glycolysis in cocultured MCF7 cells, and the component analysis of glycolysis-related genes revealed that the second most abundant component after the cytoplasm was extracellular exosomes. In addition, proteomic analysis of EVs showed that the key proteins capable of phosphorylating PKM2 were present as cargo inside MDA-MB-231 cell-derived EVs. CONCLUSIONS The phenomena observed in this study suggest that cancer cells can induce a phenotype transition of other subtypes to an aggressive phenotype to consequently activate glucose metabolism via EVs. Therefore, this study could serve as a cornerstone for further research on interactions between cancer cells.
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Affiliation(s)
- Seo Young Kang
- Department of Nuclear Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
| | - Eun Ji Lee
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Jung Woo Byun
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea
| | - Dohyun Han
- Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, South Korea
- Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
| | - Yoori Choi
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
| | - Do Won Hwang
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
- THERABEST, Co. Inc., Seoul, South Korea
| | - Dong Soo Lee
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
- Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
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Zhu M, Li S, Li S, Wang H, Xu J, Wang Y, Liang G. Strategies for Engineering Exosomes and Their Applications in Drug Delivery. J Biomed Nanotechnol 2021; 17:2271-2297. [PMID: 34974854 DOI: 10.1166/jbn.2021.3196] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Exosomes are representative of a promising vehicle for delivery of biomolecules. Despite their discovery nearly 40 years, knowledge of exosomes and extracellular vesicles (EVs) and the role they play in etiology of disease and normal cellular physiology remains in its infancy. EVs are produced in almost all cells, containing nucleic acids, lipids, and proteins delivered from donor cells to recipient cells. Consequently, they act as mediators of intercellular communication and molecular transfer. Recent studies have shown that, exosomes are associated with numerous physiological and pathological processes as a small subset of EVs, and they play a significant role in disease progression and treatment. In this review, we discuss several key questions: what are exosomes, why do they matter, and how do we repurpose them in their strategies and applications in drug delivery systems. In addition, opportunities and challenges of exosome-based theranostics are also described and directions for future research are presented.
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Affiliation(s)
- Mengxi Zhu
- School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China
| | - Shan Li
- School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China
| | - Sanqiang Li
- School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China
| | - Haojie Wang
- School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China
| | - Juanjuan Xu
- School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China
| | - Yili Wang
- School of Basic Medicine, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Gaofeng Liang
- School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China
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21
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Russomanno P, Assoni G, Amato J, D'Amore VM, Scaglia R, Brancaccio D, Pedrini M, Polcaro G, La Pietra V, Orlando P, Falzoni M, Cerofolini L, Giuntini S, Fragai M, Pagano B, Donati G, Novellino E, Quintavalle C, Condorelli G, Sabbatino F, Seneci P, Arosio D, Pepe S, Marinelli L. Interfering with the Tumor-Immune Interface: Making Way for Triazine-Based Small Molecules as Novel PD-L1 Inhibitors. J Med Chem 2021; 64:16020-16045. [PMID: 34670084 DOI: 10.1021/acs.jmedchem.1c01409] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The inhibition of the PD-1/PD-L1 axis by monoclonal antibodies has achieved remarkable success in treating a growing number of cancers. However, a novel class of small organic molecules, with BMS-202 (1) as the lead, is emerging as direct PD-L1 inhibitors. Herein, we report a series of 2,4,6-tri- and 2,4-disubstituted 1,3,5-triazines, which were synthesized and assayed for their PD-L1 binding by NMR and homogeneous time-resolved fluorescence. Among them, compound 10 demonstrated to strongly bind with the PD-L1 protein and challenged it in a co-culture of PD-L1 expressing cancer cells (PC9 and HCC827 cells) and peripheral blood mononuclear cells enhanced antitumor immune activity of the latter. Compound 10 significantly increased interferon γ release and apoptotic induction of cancer cells, with low cytotoxicity in healthy cells when compared to 1, thus paving the way for subsequent preclinical optimization and medical applications.
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Affiliation(s)
- Pasquale Russomanno
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | - Giulia Assoni
- Department of Cellular, Computational and Integrative Biology, (CIBIO), Università degli Studi di Trento, Via Sommarive 9, Povo I-38123, Trento, Italy.,Chemistry Department, Università degli Studi di Milano, Via C. Golgi 19, Milan 20133, Italy
| | - Jussara Amato
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | - Vincenzo Maria D'Amore
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | - Riccardo Scaglia
- Chemistry Department, Università degli Studi di Milano, Via C. Golgi 19, Milan 20133, Italy
| | - Diego Brancaccio
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | - Martina Pedrini
- Chemistry Department, Università degli Studi di Milano, Via C. Golgi 19, Milan 20133, Italy
| | - Giovanna Polcaro
- Dipartimento di Medicina e Chirurgia, Ospedale "San Giovanni di Dio e Ruggi d'Aragona", Università di Salerno, Salerno 84131, Italy
| | - Valeria La Pietra
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | - Paolo Orlando
- Chemistry Department, Università degli Studi di Milano, Via C. Golgi 19, Milan 20133, Italy
| | - Marianna Falzoni
- Chemistry Department, Università degli Studi di Milano, Via C. Golgi 19, Milan 20133, Italy
| | - Linda Cerofolini
- Centro di Risonanza Magnetica, CERM, Università di Firenze, Firenze 50019, Italy
| | - Stefano Giuntini
- Centro di Risonanza Magnetica, CERM, Università di Firenze, Firenze 50019, Italy
| | - Marco Fragai
- Centro di Risonanza Magnetica, CERM, Università di Firenze, Firenze 50019, Italy
| | - Bruno Pagano
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | - Greta Donati
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
| | | | - Cristina Quintavalle
- Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy; Institute for Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples 80131, Italy
| | - Gerolama Condorelli
- Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples, Italy; Institute for Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples 80131, Italy.,Department of Molecular Medicine and Medical Biotechnology, "Federico II" University, Naples 80131, Italy
| | - Francesco Sabbatino
- Dipartimento di Medicina e Chirurgia, Ospedale "San Giovanni di Dio e Ruggi d'Aragona", Università di Salerno, Salerno 84131, Italy
| | - Pierfausto Seneci
- Chemistry Department, Università degli Studi di Milano, Via C. Golgi 19, Milan 20133, Italy
| | - Daniela Arosio
- Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC), Consiglio Nazionale delle Ricerche (CNR), Via C. Golgi 19, Milan 20133, Italy
| | - Stefano Pepe
- Dipartimento di Medicina e Chirurgia, Ospedale "San Giovanni di Dio e Ruggi d'Aragona", Università di Salerno, Salerno 84131, Italy
| | - Luciana Marinelli
- Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli 80131, Italy
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Cancer-Derived Exosomal miR-651 as a Diagnostic Marker Restrains Cisplatin Resistance and Directly Targets ATG3 for Cervical Cancer. DISEASE MARKERS 2021; 2021:1544784. [PMID: 34567283 PMCID: PMC8460390 DOI: 10.1155/2021/1544784] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/13/2021] [Indexed: 11/17/2022]
Abstract
Objective Cancer-derived exosomes can facilitate drug resistance in cervical cancer. However, the mechanisms remain elusive. Herein, we observed the roles of exosomal miR-651 in cisplatin resistance of cervical cancer. Methods Circulating miR-651 was detected in cervical cancer and healthy individuals. The diagnostic efficacy was determined. When transfected with miR-651 mimics, cisplatin resistance, apoptosis, and proliferation were assessed. The cancer-derived exosomes were separated and identified. We observed the uptake of PKH67-labeled exosomes by HeLa/S cells. After coculture with exosomes secreted by HeLa/S or HeLa/DDP cells, malignant behaviors were examined in HeLa/S cells. The interactions between ATG3 and miR-651 were validated by dual luciferase report. Biological behaviors were investigated for HeLa/S cells cocultured with exosomes secreted by miR-651 mimic-transfected HeLa/DDP cells. Results Downregulated circulating miR-651 was found in cancer subjects than healthy individuals. It possessed high sensitivity and accuracy in diagnosing cervical cancer (AUC = 0.9050). Lower miR-651 expression was confirmed in HeLa/DDP than HeLa/S cells. Forced miR-651 lessened cisplatin resistance and proliferation and elevated apoptosis in HeLa cells. ATG3 was a direct target of miR-651. The exosomes isolated from HeLa cells were rich in CD63, CD9, and CD81 proteins, thereby identifying the isolated exosomes. Exosomes secreted by HeLa/DDP cells can be absorbed by HeLa/S cells. When being cocultured with exosomes secreted by HeLa/DDP cells, malignant behaviors of HeLa/S cells were enhanced, which were ameliorated by miR-651 mimic exosomes. Conclusion Our findings showed that cancer-derived exosomal miR-651 restrained cisplatin resistance and directly targeted ATG3, indicating that exosomal miR-651 could be a therapeutic agent.
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Joudaki N, Rashno M, Asadirad A, Khodadadi A. Role of breast cancer-derived exosomes in metabolism of immune cells through PD1-GLUT1-HK2 metabolic axis. Tissue Cell 2021; 71:101576. [PMID: 34146942 DOI: 10.1016/j.tice.2021.101576] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/03/2021] [Accepted: 06/07/2021] [Indexed: 12/24/2022]
Abstract
Tumor cells modulate immune responses by secreting exosomes. Tumor exosomes can affect the metabolism of immune cells and increase immune inhibitory molecules such as programmed cell death protein 1 (PD-1). PD-1 inhibits the glycolysis pathway in immune cells. We investigated the role of tumor exosomes in how metabolic changes occur through the PD1-GLUT1-HK2 metabolic axisin peripheral blood mononuclear cells (PBMCs). The MDA-MB-231 cell line was cultured, serum samples from breast cancer patients were collected, and exosomes purified from serum samples and the MDA-MB-231 cell line. PBMCs were treated with purified exosomes for 72 h and, the expression of PD1-GLUT1-HK2 genes was measured by real-time PCR. Our study results showed relative expression of the HK2 gene in both groups treated with MDA-MB-231 cell line exosomes and serum exosomes of breast cancer patients was significantly increased compared to the control group (p < 0.0001). Also, the relative expression of the PD1 gene and GLUT1 gene showed a significant increase compared to the control group only in the group treated with MDA-MB-231 cell line exosomes (p < 0.0001). Therefore, Breast cancer exosomes increased the expression of key genes in the glycolysis pathway, increasing the glycolysis pathway in PBMCs. Increased expression of PD-1 could not prevent the expression of critical genes in the glycolysis pathway as in previous studies.
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Affiliation(s)
- Nazanin Joudaki
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohammad Rashno
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Ali Asadirad
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Ali Khodadadi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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24
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Li YC, Zheng J, Wang XZ, Wang X, Liu WJ, Gao JL. Mesenchymal stem cell-derived exosomes protect trabecular meshwork from oxidative stress. Sci Rep 2021; 11:14863. [PMID: 34290351 PMCID: PMC8295363 DOI: 10.1038/s41598-021-94365-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 07/09/2021] [Indexed: 12/22/2022] Open
Abstract
This study aims to investigate the beneficial effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on trabecular meshwork cells under oxidative stress and predict candidate genes associated with this process. Trabecular meshwork cells were pretreated with BMSC-derived exosomes for 24 h, and exposed to 0.1 mM H2O2 for 6 h. Survival rate of trabecular meshwork cells was measured with CCK-8 assay. Production of intracellular reactive oxygen species (iROS) was measured using a flow cytometer. RT-PCR and ELISA were used to detect mRNA and protein levels of inflammatory cytokines and matrix metalloproteinases (MMPs). Sequencing of RNA and miRNA for trabecular meshwork cells from Exo and control groups was performed on BGISEQ500 platform. Phenotypically, pretreatment of BMSC-derived exosomes improves survival rate of trabecular meshwork cells exposed to H2O2, reduces production of iROS, and inhibits expression of inflammatory cytokines, whereas increases expression of MMPs. There were 23 miRNAs, 307 lncRNAs, and 367 mRNAs differentially expressed between Exo and control groups. Exosomes derived from BMSCs may protect trabecular meshwork cells from oxidative stress. Candidate genes responsible for beneficial effects, such as DIO2 and HMOX1, were predicted.
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Affiliation(s)
- Ying-Chao Li
- Department of Ophthalmology, Liaocheng People's Hospital, Cheeloo College of Medicine, Shandong University, Liaocheng, 252000, Shandong, China
- Department of Ophthalmology, Taian City Central Hospital, Taian, 271000, Shandong, China
| | - Juan Zheng
- Joint Laboratory for Translational Medicine Research, Beijing Institute of Genomics, Chinese Academy of Sciences & Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China
| | - Xi-Zi Wang
- Joint Laboratory for Translational Medicine Research, Beijing Institute of Genomics, Chinese Academy of Sciences & Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China
| | - Xin Wang
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China
| | - Wen-Jing Liu
- Department of Ophthalmology, Taian City Central Hospital, Taian, 271000, Shandong, China
| | - Jian-Lu Gao
- Department of Ophthalmology, Liaocheng People's Hospital, Cheeloo College of Medicine, Shandong University, Liaocheng, 252000, Shandong, China.
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China.
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25
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Umwali Y, Yue CB, Gabriel ANA, Zhang Y, Zhang X. Roles of exosomes in diagnosis and treatment of colorectal cancer. World J Clin Cases 2021; 9:4467-4479. [PMID: 34222415 PMCID: PMC8223826 DOI: 10.12998/wjcc.v9.i18.4467] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/15/2021] [Accepted: 05/06/2021] [Indexed: 02/06/2023] Open
Abstract
Exosomes are extracellular vesicles that mediate intercellular communication. They contain different molecules, such as DNA, RNA, lipid, and protein, playing essential roles in the pathogenesis of colorectal cancer (CRC). Exosomes derived from CRC are implicated in tumorigenesis, chemotherapy resistance, and metastasis. Besides, they can enhance CRC progression by increasing tumor cell proliferation, reducing apoptosis mechanistically through altering particular essential regulatory genes, or controlling several signaling pathways. Therefore, exosomes derived from CRC are essential biomarkers and can be used in the diagnosis. Indeed, it is crucial to understand the role of exosomes in CRC, which is necessary to develop diagnostic and therapeutic strategies for early detection and treatment. In the present review, we discuss the roles of exosomes in the diagnosis and treatment of CRC.
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Affiliation(s)
- Yvette Umwali
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Cong-Bo Yue
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Abakundana Nsenga Ariston Gabriel
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
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26
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Li Y, Qu H, Ji J, Wang Y, Liu T, He J, Wang J, Shu D, Luo C. Characterization of the exosomes in the allantoic fluid of the chicken embryo. CANADIAN JOURNAL OF ANIMAL SCIENCE 2021. [DOI: 10.1139/cjas-2020-0130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The embryo stage is critical for chicken development. Numerous studies have been conducted to clarify the dynamic changes and functions of various proteins and the composition of amino acids during embryo development. However, the physiological characteristics of extraembryonic fluid (allantoic and amniotic), especially allantoic fluid (AF), remain largely unexplored; furthermore, how information is transmitted from embryonic fluid is unknown. In this study, AF-derived exosomes ranging from 60 to 160 nm in diameter from fertilized eggs at 13 d of incubation of fast-growth chickens (WG chicken), medium-growth chickens (Silky N4 chicken), and slow-growth chickens (Huiyang Beard chicken) were isolated and purified by different ultra-centrifugations and further verified by transmission electron microscopy and a flow nano-analyzer. Expression of the exosomal positive biomarkers of ALIX and HSP70 as well as lack of the epithelium marker GRP78 was observed by Western blotting. In addition, small RNA sequencing revealed that AF-derived exosomes at 13 d of incubation contained a large number of known miRNAs (32.62%–65.83%). The top 10 most abundant and co-expressed miRNAs were primarily related to development, growth, and immunity. In addition, AF-derived exosomes promoted DF-1 cell migration. These findings broadened our understanding of the characteristic of AF-derived exosomes.
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Affiliation(s)
- Ying Li
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Hao Qu
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Jian Ji
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Yan Wang
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Tianfei Liu
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Jingyi He
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Jie Wang
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Dingming Shu
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
| | - Chenglong Luo
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
- Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, State Key Laboratory of Livestock and Poultry Breeding, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangdong, Guangzhou 510640, China
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Raffaniello RD. Rab3 proteins and cancer: Exit strategies. J Cell Biochem 2021; 122:1295-1301. [PMID: 33982832 DOI: 10.1002/jcb.29948] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/19/2021] [Indexed: 11/08/2022]
Abstract
Rab proteins are GTPases involved in all stages of vesicular transport and membrane fusion in mammalian cells. Individual Rab proteins localize to specific cellular organelles and regulate a specific membrane trafficking pathway. Recent studies suggest an important role for Rab proteins in cancer. Rab3 isoforms (Rab3A, Rab3B, Rab3C, and Rab3D) are expressed almost exclusively in neurons and secretory cells. In this review, the role of Rab3 isoforms in a variety of tumor types is discussed. Of the four Rab3 isoforms, Rab3D has been studied most extensively in cancer cells and this isoform appears to play an oncogenic role in breast, colon, esophageal, skin, and brain tumors. Overexpression of Rab3A and Rab3C was observed in gliomas and colon cancers, respectively. Increased expression of the Rab3 isoforms is related to increased proliferation, migration, and invasiveness. Moreover, high Rab3 isoform levels are often associated with decreased survival and advanced pathological stage in clinical samples. Rab3 isoform-dependent activation of the AKT pathway has been observed in several studies. Although the effects of Rab3 isoforms on cancer cell growth and function have been examined in many tumor types, a number of important questions remain. Are the Rab3-positive vesicles in cancer cells actually secretory in nature? If so, are the contents of these vesicles secreted in a regulated or constitutive manner? How does Rab3-regulated secretion affect cellular signaling and tumor growth? Finally, can Rab3 isoforms be therapeutically manipulated in cancer cells? The fact that knockout of a single Rab3 isoform does not affect viability, at least in mouse models, suggests that targeting of these proteins may be a safe and effective treatment strategy for tumor cells expressing any of the Rab3 isoforms.
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Affiliation(s)
- Robert D Raffaniello
- Department of Medical Laboratory Sciences, Hunter College, School of Arts and Sciences, New York, New York, USA
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28
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Elewaily MI, Elsergany AR. Emerging role of exosomes and exosomal microRNA in cancer: pathophysiology and clinical potential. J Cancer Res Clin Oncol 2021; 147:637-648. [PMID: 33511427 DOI: 10.1007/s00432-021-03534-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Exosomes are extracellular nanometric vesicles used by cells to communicate with each other. They are responsible for many pathological conditions, including tumors by transferring regulatory biomolecules that impact target cell activity. Because of their high concentration in exosomes compared with parental cells and the rest of exosomal content, specificity to the cell of origin, and their well-organized sorting mechanism, microRNAs (miRNAs) are thought to be the most potent exosomes cargo and used by scientists to track exosomes and to detect cell activity changes and prognosis in cancer early. PURPOSE In this review, the results of studies examining the role of exosomes in cancer pathophysiology and their clinical potential are discussed in detail. Tumor-derived exosomes (TDEs) mediate the dynamic changes of cancer growth and invasion, including local microenvironment remodeling, distance metastasis, angiogenesis, and tumor-associated immunosuppression. They also contribute to hypoxia-induced tumor progression and cancer cell drug resistance. As a result of exosomes being present in all body fluids, it is possible to have early accessible and less-invasive diagnostic and prognostic measures by forming a table for each cancer type and its matched specific miRNAs. Under testing, available therapeutic uses of exosomes include interference of exosomes biogenesis, secretion, or uptake, and recruitment of exosomes as target-specific drug delivery vehicles, and immunostimulatory agents for both cancer patients and healthy population to avoid cancer development from the start. CONCLUSION These data suggest that exosomes and exosomal microRNA are directly related to cancer progression mechanisms, and could be used in cancer early diagnosis, prognosis, and therapy.
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Affiliation(s)
| | - Alyaa R Elsergany
- Internal Medicine Department, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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29
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Galbiati S, Damin F, Brambilla D, Ferraro L, Soriani N, Ferretti AM, Burgio V, Ronzoni M, Vago R, Sola L, Chiari M. Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients. Pharmaceuticals (Basel) 2021; 14:ph14020128. [PMID: 33562158 PMCID: PMC7915475 DOI: 10.3390/ph14020128] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 02/02/2021] [Accepted: 02/03/2021] [Indexed: 12/30/2022] Open
Abstract
It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.
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Affiliation(s)
- Silvia Galbiati
- Complications of Diabetes Units, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
- Correspondence: (S.G.); (F.D.)
| | - Francesco Damin
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy; (D.B.); (L.F.); (A.M.F.); (L.S.); (M.C.)
- Correspondence: (S.G.); (F.D.)
| | - Dario Brambilla
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy; (D.B.); (L.F.); (A.M.F.); (L.S.); (M.C.)
| | - Lucia Ferraro
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy; (D.B.); (L.F.); (A.M.F.); (L.S.); (M.C.)
| | - Nadia Soriani
- Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;
| | - Anna M. Ferretti
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy; (D.B.); (L.F.); (A.M.F.); (L.S.); (M.C.)
| | - Valentina Burgio
- Dipartimento di Oncologia Medica, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (V.B.); (M.R.)
| | - Monica Ronzoni
- Dipartimento di Oncologia Medica, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (V.B.); (M.R.)
| | - Riccardo Vago
- Urological Research Institute, Division of Experimental Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy;
- Università Vita-Salute San Raffaele, 20132 Milano, Italy
| | - Laura Sola
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy; (D.B.); (L.F.); (A.M.F.); (L.S.); (M.C.)
| | - Marcella Chiari
- Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy; (D.B.); (L.F.); (A.M.F.); (L.S.); (M.C.)
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Potential miRNA biomarkers for the diagnosis and prognosis of esophageal cancer detected by a novel absolute quantitative RT-qPCR method. Sci Rep 2020; 10:20065. [PMID: 33208781 PMCID: PMC7676265 DOI: 10.1038/s41598-020-77119-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 11/04/2020] [Indexed: 12/29/2022] Open
Abstract
miRNAs are expected to become potential biomarkers in the diagnosis and prognosis of Esophageal cancer (EC). Through a series of screening, miR-34a-5p, miR-148a-3p and miR-181a-5p were selected as EC-associated miRNAs. Based on AllGlo probe, a novel absolute quantitative RT-qPCR method with high sensitivity, specificity and accuracy was established for detecting miRNAs. Then the clinical significance of these 3 miRNAs was explored with 213 patients (166 cases with EC and 47 cases with benign diseases) and 170 normal controls. Compared with normal controls, the level of miR-34a-5p increased while miR-148a-3p and miR-181a-5p decreased in EC and benign patients (P < 0.001), and the level of miR-181a-5p in early EC patients was significantly lower (P < 0.001). According to logistic regression analysis, combined detection of miR-34a-5p, miR-148a-3p and Cyfra21-1 provided the highest diagnosis efficiency of 85.07% with sensitivity and specificity reaching 85.45% and 84.71%. Compared with preoperative samples, the level of miR-34a-5p decreased while miR-148a-3p and miR-181a-5p increased in postoperative samples (P < 0.001). Collectively, this first developed, novel absolute quantitative RT-qPCR method exhibits high application value in detecting miRNAs, miR-34a-5p, miR-148a-3p and miR-181a-5p may serve as potential biomarkers in the diagnosis and prognosis of EC, and miR-181a-5p probably could serve as a new biomarker for early EC.
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Geng HY, Feng ZJ, Zhang JJ, Li GY. Exosomal CLIC1 released by CLL promotes HUVECs angiogenesis by regulating ITGβ1-MAPK/ERK axis. Kaohsiung J Med Sci 2020; 37:226-235. [PMID: 32841520 DOI: 10.1002/kjm2.12287] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 12/16/2022] Open
Abstract
Accumulating evidences have suggested that exosomes are closely associated with tumor progression by affecting cell-cell communication. Here, we aimed to investigate the roles and regulatory mechanism of exosomes released from chronic lymphocytic leukemia (CLL). The expression levels of genes and proteins in cells and exosomes were examined by quantitative real-time PCR and Western blotting, respectively. MEC-1 cell-derived exosomes were obtained and co-cultured with human umbilical vein endothelial cells (HUVECs), then the capabilities of cell proliferation, metastasis and angiogenesis of HUVECs were measured by CCK-8, wound healing, transwell and tube formation assay, respectively. Chloride intracellular channel 1 (CLIC1) was significantly increased in CLL patients and markedly enriched in exosomes secreted by CLL cells. Exosomal CLIC1 secreted from MEC-1 cells were successfully transferred into HUVECs and significantly promoted the phenotypes of proliferation, metastasis and angiogenesis of HUVECs. Mechanically, exosomal CLIC1 secreted from MEC-1 cells obviously activated MAPK/ERK signaling through upregulating integrin β1 (ITGβ1) expression in HUVECs. Furthermore, rescue experiments revealed that either silencing ITGβ1 or PD98059 treatment obviously reversed the regulatory effects of exosomal CLIC1 secreted from MEC-1 cells in HUVECs. In conclusion, CLL cell-derived exosomes accelerated HUVECs metastasis and angiogenesis through transferring CLIC1 to regulate ITGβ1-MAPK/ERK signaling, indicating that CLIC1 may be a therapeutic target of CLL exosomes in the tumor microenvironment.
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Affiliation(s)
- Hua-Yun Geng
- Department of Hematology, Liaocheng Dongchangfu People's Hospital, Liaocheng, Shandong Province, P.R. China
| | - Zhen-Jun Feng
- Department of Hematology, Liaocheng People's Hospital, Liaocheng, Shandong Province, P.R. China
| | - Jing-Jing Zhang
- Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, P.R. China
| | - Guang-Yao Li
- Department of Hematology, Liaocheng People's Hospital, Liaocheng, Shandong Province, P.R. China
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Ferreri C, Sansone A, Ferreri R, Amézaga J, Tueros I. Fatty Acids and Membrane Lipidomics in Oncology: A Cross-Road of Nutritional, Signaling and Metabolic Pathways. Metabolites 2020; 10:metabo10090345. [PMID: 32854444 PMCID: PMC7570129 DOI: 10.3390/metabo10090345] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 08/20/2020] [Accepted: 08/23/2020] [Indexed: 12/11/2022] Open
Abstract
Fatty acids are closely involved in lipid synthesis and metabolism in cancer. Their amount and composition are dependent on dietary supply and tumor microenviroment. Research in this subject highlighted the crucial event of membrane formation, which is regulated by the fatty acids' molecular properties. The growing understanding of the pathways that create the fatty acid pool needed for cell replication is the result of lipidomics studies, also envisaging novel fatty acid biosynthesis and fatty acid-mediated signaling. Fatty acid-driven mechanisms and biological effects in cancer onset, growth and metastasis have been elucidated, recognizing the importance of polyunsaturated molecules and the balance between omega-6 and omega-3 families. Saturated and monounsaturated fatty acids are biomarkers in several types of cancer, and their characterization in cell membranes and exosomes is under development for diagnostic purposes. Desaturase enzymatic activity with unprecedented de novo polyunsaturated fatty acid (PUFA) synthesis is considered the recent breakthrough in this scenario. Together with the link between obesity and cancer, fatty acids open interesting perspectives for biomarker discovery and nutritional strategies to control cancer, also in combination with therapies. All these subjects are described using an integrated approach taking into account biochemical, biological and analytical aspects, delineating innovations in cancer prevention, diagnostics and treatments.
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Affiliation(s)
- Carla Ferreri
- Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via Piero Gobetti 101, 40129 Bologna, Italy;
- Correspondence:
| | - Anna Sansone
- Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via Piero Gobetti 101, 40129 Bologna, Italy;
| | - Rosaria Ferreri
- Department of Integrated Medicine, Tuscany Reference Centre for Integrated Medicine in the hospital pathway, Pitigliano Hospital, Via Nicola Ciacci, 340, 58017 Pitigliano, Italy;
| | - Javier Amézaga
- AZTI, Food and Health, Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (J.A.); (I.T.)
| | - Itziar Tueros
- AZTI, Food and Health, Parque Tecnológico de Bizkaia, Astondo Bidea, Edificio 609, 48160 Derio, Spain; (J.A.); (I.T.)
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Figueroa AG, McKay BS. A G-Protein Coupled Receptor and Macular Degeneration. Cells 2020; 9:cells9040910. [PMID: 32276449 PMCID: PMC7226737 DOI: 10.3390/cells9040910] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 03/31/2020] [Accepted: 04/07/2020] [Indexed: 12/12/2022] Open
Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.
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Ferreri C, Sansone A, Buratta S, Urbanelli L, Costanzi E, Emiliani C, Chatgilialoglu C. The n-10 Fatty Acids Family in the Lipidome of Human Prostatic Adenocarcinoma Cell Membranes and Extracellular Vesicles. Cancers (Basel) 2020; 12:E900. [PMID: 32272739 PMCID: PMC7226157 DOI: 10.3390/cancers12040900] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 02/07/2020] [Accepted: 03/31/2020] [Indexed: 02/06/2023] Open
Abstract
A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid, a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid has attracted attention as a novel marker of cancer cell plasticity. Here, we analyzed fatty acids, including the n-10 fatty acid contents, and for the first time, compared cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 versus delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.
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Affiliation(s)
- Carla Ferreri
- Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy; (A.S.); (C.C.)
| | - Anna Sansone
- Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy; (A.S.); (C.C.)
| | - Sandra Buratta
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy; (S.B.); (L.U.); (E.C.); (C.E.)
| | - Lorena Urbanelli
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy; (S.B.); (L.U.); (E.C.); (C.E.)
| | - Eva Costanzi
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy; (S.B.); (L.U.); (E.C.); (C.E.)
| | - Carla Emiliani
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06122 Perugia, Italy; (S.B.); (L.U.); (E.C.); (C.E.)
| | - Chryssostomos Chatgilialoglu
- Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129 Bologna, Italy; (A.S.); (C.C.)
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Hou K, Li G, Zhao J, Xu B, Zhang Y, Yu J, Xu K. Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway. J Neuroinflammation 2020; 17:46. [PMID: 32014002 PMCID: PMC6998092 DOI: 10.1186/s12974-020-1725-8] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 01/24/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. METHODS We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. RESULTS The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis. CONCLUSION BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.
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Affiliation(s)
- Kun Hou
- Department of Neurosurgery, The First Hospital of Jilin University, No. 1 Xinmin Avenue, Changchun, 130021, Jilin, People's Republic of China
| | - Guichen Li
- Department of Neurology, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China
| | - Jinchuan Zhao
- Department of Neurosurgery, The First Hospital of Jilin University, No. 1 Xinmin Avenue, Changchun, 130021, Jilin, People's Republic of China
| | - Baofeng Xu
- Department of Neurosurgery, The First Hospital of Jilin University, No. 1 Xinmin Avenue, Changchun, 130021, Jilin, People's Republic of China
| | - Yang Zhang
- Department of Neurosurgery, The First Hospital of Jilin University, No. 1 Xinmin Avenue, Changchun, 130021, Jilin, People's Republic of China
| | - Jinlu Yu
- Department of Neurosurgery, The First Hospital of Jilin University, No. 1 Xinmin Avenue, Changchun, 130021, Jilin, People's Republic of China.
| | - Kan Xu
- Department of Neurosurgery, The First Hospital of Jilin University, No. 1 Xinmin Avenue, Changchun, 130021, Jilin, People's Republic of China.
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Zhou K, Guo S, Li F, Sun Q, Liang G. Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies. Front Cell Dev Biol 2020; 8:569219. [PMID: 33178688 PMCID: PMC7593554 DOI: 10.3389/fcell.2020.569219] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 08/27/2020] [Indexed: 12/15/2022] Open
Abstract
As a classical immune checkpoint molecule, PD-L1 on the surface of tumor cells plays a pivotal role in tumor immunosuppression, primarily by inhibiting the antitumor activities of T cells by binding to its receptor PD-1. PD-1/PD-L1 inhibitors have demonstrated unprecedented promise in treating various human cancers with impressive efficacy. However, a significant portion of cancer patients remains less responsive. Therefore, a better understanding of PD-L1-mediated immune escape is imperative. PD-L1 can be expressed on the surface of tumor cells, but it is also found to exist in extracellular forms, such as on exosomes. Recent studies have revealed the importance of exosomal PD-L1 (ExoPD-L1). As an alternative to membrane-bound PD-L1, ExoPD-L1 produced by tumor cells also plays an important regulatory role in the antitumor immune response. We review the recent remarkable findings on the biological functions of ExoPD-L1, including the inhibition of lymphocyte activities, migration to PD-L1-negative tumor cells and immune cells, induction of both local and systemic immunosuppression, and promotion of tumor growth. We also discuss the potential implications of ExoPD-L1 as a predictor for disease progression and treatment response, sensitive methods for detection of circulating ExoPD-L1, and the novel therapeutic strategies combining the inhibition of exosome biogenesis with PD-L1 blockade in the clinic.
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Affiliation(s)
- Kaijian Zhou
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Shu Guo
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Shu Guo,
| | - Fei Li
- Department of Pharmaceutical Science, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Qiang Sun
- Department of Plastic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Guoxin Liang
- Cancer Therapy Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, China
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