• cancer microenvironment
• reprogramming

• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/pathology
• Humans
• Tumor Microenvironment
• Neoplasms/pathology
• Neoplasms/genetics
• Animals
• Extracellular Matrix/metabolism

• Lewis lung carcinoma karyotype
• angiogenesis
• cancer
• human mesenchymal stem cells
• tumor growth and metastasis

• Humans
• Mice
• Animals
• Carcinoma, Lewis Lung/pathology
• Mice, Inbred C57BL
• Lung Neoplasms/pathology
• Mesenchymal Stem Cells

• 2021YFF0502900 National Key R&D Program of China
• 62127819 National Natural Science Foundation of China
• 61835009 National Natural Science Foundation of China
• ZDSYS20210623092006020 Shenzhen Key Laboratory of Photonics and Biophotonics
• JCYJ20220818100202005 Shenzhen Science and Technology Program
• 2.2.5.443 National Academy of Sciences of Ukraine

• biomimetic materials
• bone regeneration
• mineralized materials
• osteosarcoma
• segmental defect

• Humans
• Animals
• Mice
• Cisplatin/pharmacology
• Cisplatin/therapeutic use
• Disease Models, Animal
• Osteosarcoma/drug therapy
• Bone Regeneration
• Bone Neoplasms/drug therapy
• Bone Neoplasms/pathology
• Bone Neoplasms/surgery

• Men of Distinction Foundation

• COVID-19
• immune modulation
• lung cancer
• mesenchymal stem cells
• severe pneumonia
• tissue repairment

• Humans
• Female
• Aged
• COVID-19/etiology
• SARS-CoV-2
• Lung Neoplasms/etiology
• Radiation Pneumonitis/etiology
• Radiation Pneumonitis/therapy
• Pandemics
• Mesenchymal Stem Cell Transplantation/adverse effects
• Neoplasm Recurrence, Local
• Mesenchymal Stem Cells

• OCT
• cryoinjury
• mesothelial reaction
• pleura

• 2014-0006286 National Research Foundation of Korea

• cancer
• mesenchymal stem cells
• stroma
• therapies
• tumor microenvironment

• Humans
• Carcinogenesis
• Mesenchymal Stem Cells
• Melanoma
• Lung Neoplasms
• Multipotent Stem Cells
• Tumor Microenvironment

• Glioma
• Glioma-resident mesenchymal stem cells
• Mesenchymal stem cells
• Tumor microenvironment
• Tumor-promoting

• Humans
• Interleukin-6/metabolism
• Glioma/metabolism
• Mesenchymal Stem Cells/metabolism
• MicroRNAs/metabolism
• Signal Transduction
• Tumor Microenvironment
• Forkhead Transcription Factors

• cancer therapy
• drug-delivery systems
• multicellular spheroids
• scaffold-based model and microfluids devices
• scaffold-free model

• 001 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

• Mycobacterium tuberculosis
• bacterial heterogeneity
• host-pathogen interaction
• persistence
• persisters
• phagocytosis
• phagosome acidification

Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.

• Cancer treatment
• Heat transfer
• Hyperthermia
• Hyperthermic intraperitoneal chemotherapy
• Peritoneal cancer
• Peritoneal surface malignancy
• Prognosis
• Survival
• Thermodynamic model

Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells. The aim of this review is to show the most contemporary knowledge concerning the biology of ovarian cancer stem cells (OCSCs) and their impact on chemo-resistance and prognosis in ovarian cancer patients, as well as to present the treatment options targeted exclusively on the OCSCs. The review presents data concerning the role of cancer stem cells in general and then concentrates on OCSCs. The surface and intracellular OCSCs markers and their meaning both for cancer biology and clinical prognosis, signaling pathways specifically activated in OCSCs, the genetic and epigenetic regulation of OCSCs function including the recent studies on the non-coding RNA regulation, cooperation between OCSCs and the tumor microenvironment (ovarian cancer niche) including very specific environment such as ascites fluid, the role of shear stress, autophagy and metabolic changes for the function of OCSCs, and finally mechanisms of OCSCs escape from immune surveillance, are described and discussed extensively. The possibilities of anti-OCSCs therapy both in experimental settings and in clinical trials are presented, including the recent II phase clinical trials and immunotherapy. OCSCs are a unique population of cancer cells showing a great plasticity, self-renewal potential and resistance against anti-cancer treatment. They are responsible for the progression and recurrence of the tumor. Several completed and ongoing clinical trials have tested different anti-OCSCs drugs which, however, have shown unsatisfactory efficacy in most cases. We propose a novel approach to ovarian cancer diagnosis and therapy.

• cancer stem cells
• ovarian cancer
• ovarian cancer stem cells
• therapy

• Carcinoma, Ovarian Epithelial/pathology
• Drug Resistance, Neoplasm
• Epigenesis, Genetic
• Female
• Humans
• Neoplastic Stem Cells/metabolism
• Ovarian Neoplasms/genetics
• Signal Transduction
• Tumor Microenvironment

• DNA methylation
• cancer epigenetics
• drug resistance
• epigenetic therapy
• histone modifications
• non-coding RNA
• ovarian cancer

• DNA Methylation
• Drug Resistance, Neoplasm/genetics
• Epigenesis, Genetic
• Female
• Humans
• Neoplasm Recurrence, Local/genetics
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/pathology
• Tumor Microenvironment/genetics

• MHA/Coll scaffold
• Osteosarcoma
• biomimetic
• bone regeneration
• chemotherapy
• osteogenesis

• Cancer progression
• Cytokine
• Mesenchymal stem cells
• Therapeutic resistance
• Tumor microenvironment

• Cancer treatment
• Cell therapy
• Gene therapy
• Regenerative medicine
• Tissue engineering

Mesenchymal stem cells (MSCs) play a central role in the intercellular signaling within the tumor microenvironment (TME), exchanging signals with cancer cells and tumor stromal cells, such as cancer-associated fibroblasts and inflammatory mononuclear cells. Research attributes both pro-tumor and anti-tumor actions to MSCs; however, evidence indicates that MSCs specific effect on the tumor depends on the source of the MSCs and the type of tumor. There are consistent data proving that MSCs from reproductive tissues, such as the uterus, umbilical cord or placenta, have potent anti-tumor effects and tropism towards tumor tissues. More interestingly, products derived from MSCs, such as secretome or extracellular vesicles, seem to reproduce the effects of their parental cells, showing a potential advantage for clinical treatments by avoiding the drawbacks associated with cell therapy. Given these perspectives, it appears necessary new research to optimize the production, safety and antitumor potency of the products derived from the MSCs suitable for oncological therapies.

• Cancer associated fibroblasts
• Macrophage associated cancer
• Tumor microenvironment
• Uterine mesenchymal stem cell

Cancer cells resistance to various therapies remains to be a key challenge nowadays. For a long time, scientists focused on tumor cells themselves for the mechanisms of acquired drug resistance. However, recent evidence showed that tumor microenvironment (TME) is essential for regulating immune escape, drug resistance, progression and metastasis of malignant cells. Reciprocal interactions between cancer cells and non-malignant cells within this milieu often reshape the TME and promote drug resistance. Therefore, advanced knowledge about these sophisticated interactions is significant for the design of effective therapeutic approaches. In this review, we highlight cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory lymphocytes (Tregs), mesenchymal stem cells (MSCs), cancer-associated adipocytes (CAAs), and tumor endothelial cells (TECs) existing in TME, as well as their multiple cross-talk with tumor cells, which eventually endows tumor cells with therapeutic resistance.

• MSCs
• CAFs
• TAMs
• antineoplastic drug resistance
• cell-cell interplays
• tumor microenvironment

• Cancer
• Chemoresistance
• Immune microenvironment
• Tumor immune response
• Tumor microenvironment
• miRNA-based therapeutics
• microRNAs

This up-to-date and in-depth review describes fibroblast-derived cells and their role within the tumor microenvironment for tumor progression. Moreover, targets for future antitumor therapies are summarized and potential aspects for future translational research are outlined. Furthermore, this review discusses the challenges and possible obstacles related to certain treatment targets.

Cells within the tumor stroma are essential for tumor progression. In particular, cancer-associated fibroblasts (CAF) and CAF precursor cells (resident fibroblasts and mesenchymal stromal cells) are responsible for the formation of the extracellular matrix in tumor tissue. Consequently, CAFs directly and indirectly mediate inflammation, metastasis, immunomodulation, angiogenesis, and the development of tumor chemoresistance, which is orchestrated by complex intercellular cytokine-mediated crosstalk. CAFs represent a strategic target in antitumor therapy but their heterogeneity hinders effective treatment regimes. In-depth understanding of CAF subpopulations and knowledge of specific functions in tumor progression will ultimately result in more specific and effective cancer treatments. This review provides a detailed description of CAFs and CAF precursor cells and summarizes possible treatment strategies as well as molecular targets of these cells in antitumor therapies.

• cancer
• cancer-associated fibroblasts
• crosstalk
• fibroblast
• mesenchymal stromal cells
• tumor
• tumor microenvironment

• Angiogenesis
• Cancer-associated fibroblasts
• Immunosuppression
• Mesenchymal stem cells
• Metastasis

• Animals
• Apoptosis
• Cytokines/metabolism
• Humans
• Immunity
• Mesenchymal Stem Cells/metabolism
• Neoplasms/immunology
• Neoplasms/metabolism
• Neoplasms/pathology
• Tumor Microenvironment/immunology

• LY18H060013 Nature Science Foundation of Zhejiang Province
• LGF18H060006 Fundamental Research Program of Public Good in Zhejiang Province
• LGF20H060010 Fundamental Research Program of Public Good in Zhejiang Province
• Nature Science Foundation of Zhejiang Province
• Fundamental Research Program of Public Good in Zhejiang Province

• Epithelial-to-mesenchymal transition
• Hepatocyte growth factor
• Melanoma
• Mesenchymal stromal cells
• Metastasis

• BET inhibitors
• Waldenström macroglobulinemia
• epigenetics
• panobinostat
• venetoclax

Bone marrow derived cells (BMDCs) play a wide variety of pro- and anti-tumorigenic roles in the tumor microenvironment (TME) and in the metastatic process. In response to chemotherapy, the anti-tumorigenic function of BMDCs can be enhanced due to chemotherapy-induced immunogenic cell death. However, in recent years, a growing body of evidence suggests that chemotherapy or other anti-cancer drugs can also facilitate a pro-tumorigenic function in BMDCs. This includes elevated angiogenesis, tumor cell proliferation and pro-tumorigenic immune modulation, ultimately contributing to therapy resistance. Such effects do not only contribute to the re-growth of primary tumors but can also support metastasis. Thus, the delicate balance of BMDC activities in the TME is violated following tumor perturbation, further requiring a better understanding of the complex crosstalk between tumor cells and BMDCs. In this review, we discuss the different types of BMDCs that reside in the TME and their activities in tumors following chemotherapy, with a major focus on their pro-tumorigenic role. We also cover aspects of rationally designed combination treatments that target or manipulate specific BMDC types to improve therapy outcomes.

• chemotherapy
• host response
• immune cells
• metastasis

• IL-9
• Oxford 40 ligand
• T regulatory cell
• TGFβ1
• mast cell

• ERK
• chemoresistance
• flavonoid
• ovarian cancer

• Hyperthermic intra peritoneal chemotherapy
• Microenvironment
• Ovarian cancer
• Resistance
• Survival

The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies.

• cell therapy
• stem cell microenvironment
• tumour microenvironment
• tumour targeting

• Mesenchymal stem/stromal cells
• extracellular vesicles
• fibrosis
• hepatocellular carcinoma
• liver diseases
• regenerative medicine.

Despite the different strategies used to treat ovarian cancer, around 70% of women/patients eventually fail to respond to the therapy. Cancer stem cells (CSCs) play a role in the treatment failure due to their chemoresistant properties. This capacity to resist chemotherapy allows CSCs to interact with different components of the tumor microenvironment, such as mesenchymal stem cells (MSCs), and thus contribute to tumorigenic processes. Although the participation of MSCs in tumor progression is well understood, it remains unclear how CSCs induce the pro-tumorigenic activity of MSCs in response to chemotherapy. Small extracellular vesicles, including exosomes, represent one possible way to modulate any type of cell. Therefore, in this study, we evaluate if small extracellular vesicle (sEV) derived from ovarian cancer spheroids (OCS), which are enriched in CSCs, can modify the activity of MSCs to a pro-tumorigenic phenotype. We show that sEV released by OCS in response to cisplatin induce an increase in the migration pattern of bone marrow MSCs (BM-MSCs) and the secretion interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor A (VEGFA). Moreover, the factors secreted by BM-MSCs induce angiogenesis in endothelial cells and the migration of low-invasive ovarian cancer cells. These findings suggest that cisplatin could modulate the cargo of sEV released by CSCs, and these exosomes can further induce the pro-tumorigenic activity of MSCs.

• bone marrow mesenchymal stem cells
• cancer stem cells
• cisplatin
• small extracellular vesicles
• spheroids
• tumor microenvironment

• Chemoresistant ovarian cancer; Mesenchymal stem cell; MiR-1180; Secreted frizzled-related protein 1 (SFRP1); Wnt; Glycolysis

Malignant tumors are highly heterogeneous and likely contain a subset of cancer cells termed cancer stem cells (CSCs). CSCs exist in a dynamic equilibrium with their microenvironments and the CSC phenotype is tightly regulated by both cell-intrinsic and cell-extrinsic factors including those derived from their surrounding cells or stroma. Many human solid tumors like breast, lung, colorectal and pancreatic cancers are characterized by a pronounced stromal reaction termed “the desmoplastic response.” Carcinoma-associated fibroblasts (CAFs) derived either from resident fibroblasts or tumor-infiltrating mesenchymal stem cells (MSCs) are a major component of the stroma in desmoplastic cancers. Recent studies identified subpopulations of CAFs proficient in secreting a plethora of factors to foster CSCs, tumor growth, and invasion. In addition, cytotoxic therapy can lead to the enrichment of functionally perturbed CAFs, which are endowed with additional capabilities to enhance cancer stemness, leading to treatment resistance and tumor aggressiveness. When recruited into the tumor stroma, bone-marrow-derived MSCs can promote cancer stemness by secreting a specific set of paracrine factors or converting into pro-stemness CAFs. Thus, blockade of the crosstalk of pro-stemness CAFs and MSCs with CSCs may provide a new avenue to improving the therapeutic outcome of desmoplastic tumors. This up-to-date, in-depth and balanced review describes the recent progress in understanding the pro-stemness roles of CAFs and tumor-infiltrating MSCs and the associated paracrine signaling processes. We emphasize the effects of systemic chemotherapy on the CAF/MSC–CSC interplay. We summarize various promising and novel approaches in mitigating the stimulatory effect of CAFs or MSCs on CSCs that have shown efficacies in preclinical models of desmoplastic tumors and highlight the unique advantages of CAF- or MSC-targeted therapies. We also discuss potential challenges in the clinical development of CSC- or MSC-targeted therapies and propose CAF-related biomarkers that can guide the next-generation clinical studies.

• cancer stem cells
• cancer-associated fibroblasts
• desmoplasia
• mesenchymal stem cells
• paracrine signaling

• Angiogenesis
• Immunosuppression
• Mesenchymal stem cells
• Metastasis
• Resistance

The ovarian cancer microenvironment is responsible for cancer cell growth and disease relapse. Bone marrow mesenchymal stem cells (BM-MSCs) play important roles in ovarian cancer, however, the mechanism of BM-MSCs inducing cell proliferation and glycolysis needs further research.

miRNA array was used to analyze the significant miRNAs. RT-qPCR was used to examine the level of miR-1180 and SFRP1. The western blotting was used to detect the protein level of SFRP1 and Wnt signal pathway. We utilized luciferase reporter assay to confirm the direct interaction of SFRP1 with miR-1180. MTT assay were employed to investigate the proliferation of ovarian cancer cells. ECAR, ATP assay were used to measure the glycolysis state of ovarian cancer cells.

It was demonstrated that BM-MSCs promoted ovarian cancer cell proliferation and glycolysis. The miRNA profile from the BM-MSCs indicated that miR-1180 was up-regulated in the conditioned medium of BM-MSCs. MiR-1180 could accelerate ovarian cancer cell proliferation and glycolysis. We also found that up-regulation of miR-1180 activated Wnt signaling by targeting SFRP1 in ovarian cancer cells.

The study demonstrated that miR-1180 was a critical miRNA mediating BM-MSCs induced cell proliferation and glycolysis and could be a new target in ovarian cancer therapy.

• Cell proliferation
• Glycolysis
• Ovarian cancer
• SFRP1
• miR-1180

Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity. Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.

• Ovarian cancer
• Tumor environment
• Peritoneal effusions
• Ascites
• Dissemination
• Multicellular spheroids

• biomarkers
• cancer
• chemotherapy
• mesenchymal stem cells
• platinuminduced fatty acids

• DNA methylation
• chromatin remodeling
• epigenetics
• histone modifications
• non-coding RNAs
• ovarian cancer
• tumor microenvironment

• 458788 (K.P.N.) Ovarian Cancer Research Fund Alliance
• (K.P.N.) Leo and Anne Albert Charitable Trust
• (Y.K.) Indiana Clinical and Translational Sciences Institute Grant Award

Immunotherapy for cervical cancer with type I interferon (IFN) is limited because of the cytotoxicity that accompanies the high doses that are administered. In this study, we investigated the utilization of amniotic fluid-derived mesenchymal stem cells (AF-MSCs) as a means for delivering IFNα to local tumor sites for the suppression of cervical cancer in a mouse model using HeLa cell xenografts.

The tumor tropism ability of AF-MSCs and AF-MSCs genetically modified to overexpress IFNα (IFNα-AF-MSCs) was examined through Transwell in vitro and through fluorescent images and immunohistochemistry in a mouse model. Tumor size and tumor apoptosis were observed to evaluate the efficacy of the targeting therapy. Mechanistically, tumor cell apoptosis was detected by cytometry and TUNEL, and oncogenic proteins c-Myc, p53, and Bcl-2 as well as microvessel density were detected by immunohistochemistry.

In this model, intravenously injected AF-MSCs selectively migrated to the tumor sites, participated in tumor construction, and promoted tumor growth. After being genetically modified to overexpress IFNα, the IFNα-AF-MSCs maintained their tumor tropism but could significantly suppress tumor growth. The restrictive efficacy of IFNα-AF-MSCs was associated with the suppression of angiogenesis, inhibition of tumor cell proliferation, and induction of apoptosis in tumor cells. Neither AF-MSCs nor IFNα-AF-MSCs trigger tumor formation.

IFNα-AF-MSC-based therapy is feasible and shows potential for treating cervical cancer, suggesting that AF-MSCs may be promising vehicles for delivering targeted anticancer therapy.

A model to predict chemotherapy response would provide a marked clinical benefit, enabling tailored treatment of oesophageal cancer, where less than half of patients respond to the routinely administered chemotherapy.

Cancer cells were established from tumour biopsies taken from individual patients about to undergo neoadjuvant chemotherapy. A 3D-tumour growth assay (3D-TGA) was developed, in which cancer cells were grown with or without supporting mesenchymal cells, then subjected to chemo-sensitivity testing using the standard chemotherapy administered in clinic, and a novel emerging HDAC inhibitor, Panobinostat.

Individual patients cancer cells could be expanded and screened within a clinically applicable timescale of 3 weeks. Incorporating mesenchymal support within the 3D-TGA significantly enhanced both the growth and drug resistance profiles of the patients cancer cells. The ex vivo drug response in the presence, but not absence, of mesenchymal cells accurately reflected clinical chemo-sensitivity, as measured by tumour regression grade. Combination with Panobinostat enhanced response and proved efficacious in otherwise chemo-resistant tumours.

This novel method of establishing individual patient oesophageal cancers in the laboratory, from small endoscopic biopsies, enables clinically-relevant chemo-sensitivity testing, and reduces use of animals by providing more refined in vitro models for pre-screening of drugs. The 3D-TGA accurately predicted chemo-sensitivity in patients, and could be developed to guide tailored patient treatment. The incorporation of mesenchymal cells as the stromal cell component of the tumour micro-environment had a significant effect upon enhancing chemotherapy drug resistance in oesophageal cancer, and could prove a useful target for future drug development.

• 3D models
• chemotherapy
• oesophageal cancer
• personalised treatment
• tumour microenvironment

• Chemoresistance
• Il-6
• Mesenchymal stromal cell
• Mouse
• Ovarian cancer

• Animals
• Antibodies, Monoclonal, Humanized/therapeutic use
• Cell Line, Tumor
• Cell Movement/drug effects
• Chemokine CCL2/genetics
• Chemokine CCL2/metabolism
• Chemokine CCL5/genetics
• Chemokine CCL5/metabolism
• Coculture Techniques
• Female
• Focal Adhesion Kinase 2/genetics
• Focal Adhesion Kinase 2/metabolism
• Humans
• Interleukin-6/genetics
• Interleukin-6/metabolism
• Mice
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/metabolism
• Signal Transduction/drug effects

During tumorigenesis and development, participation of the tumor microenvironment is not negligible. As an important component in the tumor microenvironment, mesenchymal stem cells (MSCs) have been corroborated to mediate proliferation, metastasis, and drug resistance in many cancers, including osteosarcoma. What’s more, because of tumor site tropism, MSCs can be engineered to be loaded with therapeutic agents so that drugs can be precisely delivered to tumor lesions. In this review, we mainly discuss recent advances concerning the functions of MSCs in osteosarcoma and their possible clinical applications in the future.

• Clinical applications
• Drug resistance
• MSCs
• Metastasis
• Osteosarcoma

• Tumor microenvironment (TME)
• cancer stem cells (CSCs)
• chemoresistance
• drug delivery approaches
• immune infiltrates

About 8 % of the human genome consists of human endogenous retroviruses (HERVs), which are relicts of ancient exogenous retroviral infections incurred during evolution. Although the majority of HERVs have functional gene defects or epigenetic modifications, many of them are still able to produce retroviral proteins that have been proposed to be involved in cellular transformation and cancer development.

We found that, in chemo-resistant U87^RETO glioblastoma cells, cytotoxic stress induced by etoposide promotes accumulation and large-scale fission of mitochondria, associated with the detection of HERV-WE₁ (syncytin-1) and HERV-FRD₁ (syncytin-2) in these organelles. In addition, mitochondrial preparations also contained the corresponding receptors, i.e. ASCT2 and MFSD2. We clearly demonstrated that mitochondria associated with HERV-proteins were shuttled between adjacent cancer cells not only via tunneling tubes, but also by direct cellular uptake across the cell membrane. Furthermore, anti-syncytin-1 and anti-syncytin-2 antibodies were able to specifically block this direct cellular uptake of mitochondria even more than antibodies targeting the cognate receptors.

Here, we suggest that the association of mitochondria with syncytin-1/syncytin-2 together with their respective receptors could represent a novel mechanism of cell-to-cell transfer. In chemotherapy-refractory cancer cells, this might open up attractive avenues to novel mitochondria-targeting therapies.

• human endogenous retroviruses (HERVs)
• intercellular mitochondrial transfer
• mitochondria
• syncytin-1/2 receptors

• Animals
• Bone Marrow Cells/cytology
• Carcinogenesis/pathology
• Carcinoma, Hepatocellular/pathology
• Disease Models, Animal
• Humans
• Liver Neoplasms/pathology
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/cytology
• Rats
• Umbilical Cord/cytology

Ovarian cancer is one of the most important causes of cancer-related death among women in the world. Despite advances in ovarian cancer treatment, 70–80% of women who initially respond to therapy eventually relapse and die. There is evidence that a small population of cells within the tumors called cancer stem cells (CSCs) could be responsible for treatment failure due to their enhanced chemoresistance and tumorigenicity. These cells reside in a niche that maintains the principal properties of CSCs. These properties are associated with the capacity of CSCs to interact with different cells of the tumor microenvironment including mesenchymal stem cells, endothelial cells, immune cells, and fibroblasts, promoting cancer progression. This interaction can be mediated by cytokines, growth factors, lipids, and/or extracellular vesicles released in the CSC niche. In this review, we will discuss how the interaction between ovarian CSCs and the tumor microenvironment can contribute to the maintenance of the CSC niche and consequently to tumor progression in ovarian cancer.

• Adipose stromal cells
• Adipose tissue
• Cell movement
• Interleukin-6
• Ovarian neoplasms

• Abdominal Fat/cytology
• Biomarkers
• Cell Communication
• Cell Differentiation
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation/drug effects
• Cells, Cultured
• Female
• Humans
• Immunophenotyping
• Interleukin-6/metabolism
• Janus Kinase 2/metabolism
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/pathology
• Phenotype
• Pyridines/pharmacology
• STAT3 Transcription Factor/metabolism
• Signal Transduction/drug effects
• Stromal Cells/cytology
• Stromal Cells/metabolism
• Tyrphostins/pharmacology