Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Hu J, Li G, Zhang P, Zhuang X, Hu G. A CD44v+ subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity. Cell Death Dis. 2017;8:e2679. [PMID: 28300837 PMCID: PMC5386565 DOI: 10.1038/cddis.2017.72] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 01/20/2017] [Accepted: 01/30/2017] [Indexed: 12/11/2022]

For:	Hu J, Li G, Zhang P, Zhuang X, Hu G. A CD44v+ subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity. Cell Death Dis. 2017;8:e2679. [PMID: 28300837 PMCID: PMC5386565 DOI: 10.1038/cddis.2017.72] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 01/20/2017] [Accepted: 01/30/2017] [Indexed: 12/11/2022]

Number

Cited by Other Article(s)

Liu C, Xia S, Wang B, Li J, Wang X, Ren Y, Zhou X. Osteopontin promotes tumor microenvironment remodeling and therapy resistance. Cancer Lett 2025;617:217618. [PMID: 40058726 DOI: 10.1016/j.canlet.2025.217618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/15/2025]

Affiliation(s)

Chao Liu Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China
Shunjin Xia Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China
Bo Wang Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China
Jiayong Li Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China
Xuyan Wang Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China
Yu Ren Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Xuan Zhou Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China.

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Ge QM, Hu QH, Liu JX, Min YL, Liang RB, Li B, Shi WQ, Lin Q, Yuan Q, Li QY, Shao Y. Cancer antigen 153: A risk factor for ocular metastases in patients with breast cancer. Exp Ther Med 2024;28:421. [PMID: 39301252 PMCID: PMC11412098 DOI: 10.3892/etm.2024.12710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 12/19/2022] [Indexed: 09/22/2024] Open

Xiao W, Xu C. Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review). Oncol Lett 2024;28:521. [PMID: 39268159 PMCID: PMC11391256 DOI: 10.3892/ol.2024.14654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 07/04/2024] [Indexed: 09/15/2024] Open

Preston SEJ, Dahabieh MS, Flores González RE, Gonçalves C, Richard VR, Leibovitch M, Dakin E, Papadopoulos T, Lopez Naranjo C, McCallum PA, Huang F, Gagnon N, Perrino S, Zahedi RP, Borchers CH, Jones RG, Brodt P, Miller WH, del Rincón SV. Blocking tumor-intrinsic MNK1 kinase restricts metabolic adaptation and diminishes liver metastasis. SCIENCE ADVANCES 2024;10:eadi7673. [PMID: 39270021 PMCID: PMC11397505 DOI: 10.1126/sciadv.adi7673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/07/2024] [Indexed: 09/15/2024]

Affiliation(s)

Samuel E. J. Preston Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Michael S. Dahabieh Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA
Raúl Ernesto Flores González Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Christophe Gonçalves Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Vincent R. Richard Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Matthew Leibovitch MUHC Research Institute, McGill University Health Centre, Montréal, QC, Canada
Eleanor Dakin Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Theodore Papadopoulos Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Carolina Lopez Naranjo Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Paige A. McCallum Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Fan Huang Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Natascha Gagnon Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Stephanie Perrino MUHC Research Institute, McGill University Health Centre, Montréal, QC, Canada
René P. Zahedi Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, Canada Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada CancerCare Manitoba, Winnipeg, MB, Canada
Christoph H. Borchers Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada Segal Cancer Proteomics Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada Department of Pathology, McGill University, Montréal, QC, Canada
Russell G. Jones Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA
Pnina Brodt MUHC Research Institute, McGill University Health Centre, Montréal, QC, Canada Departments of Surgery, Oncology and Medicine, McGill University, Montréal, QC, Canada
Wilson H. Miller Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
Sonia V. del Rincón Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC, Canada Gerald Bronfman Department of Oncology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada

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Kamalabadi Farahani M, Farjadmehr M, Atashi A, Momeni A, Behzadifard M. Concise review: breast cancer stems cells and their role in metastases. Ann Med Surg (Lond) 2024;86:5266-5275. [PMID: 39238997 PMCID: PMC11374310 DOI: 10.1097/ms9.0000000000002270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 06/04/2024] [Indexed: 09/07/2024] Open

Panda VK, Mishra B, Nath AN, Butti R, Yadav AS, Malhotra D, Khanra S, Mahapatra S, Mishra P, Swain B, Majhi S, Kumari K, Radharani NNV, Kundu GC. Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation. Biomedicines 2024;12:1527. [PMID: 39062100 PMCID: PMC11274826 DOI: 10.3390/biomedicines12071527] [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: 05/11/2024] [Revised: 06/22/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024] Open

Affiliation(s)

Venketesh K. Panda School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Barnalee Mishra School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Angitha N. Nath School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Ramesh Butti Division of Hematology and Oncology, Department of Internal Medicine, Southwestern Medical Center, University of Texas, Dallas, TX 75235, USA;
Amit Singh Yadav Biomedical Centre, Faculty of Medicine, Lund University, 223 62 Lund, Sweden; (A.S.Y.); (N.N.V.R.)
Diksha Malhotra School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Sinjan Khanra School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Samikshya Mahapatra School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Priyanka Mishra School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Biswajit Swain School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Sambhunath Majhi School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
Kavita Kumari School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.)
N. N. V. Radharani Biomedical Centre, Faculty of Medicine, Lund University, 223 62 Lund, Sweden; (A.S.Y.); (N.N.V.R.)
Gopal C. Kundu School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India; (V.K.P.); (B.M.); (A.N.N.); (D.M.); (S.K.); (S.M.); (P.M.); (B.S.); (S.M.); (K.K.) Kalinga Institute of Medical Sciences (KIMS), KIIT Deemed to be University, Bhubaneswar 751024, India

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Wang D, Keyoumu K, Yu R, Wen D, Jiang H, Liu X, Di X, Zhang S. Extracellular matrix marker LAMC2 targets ZEB1 to promote TNBC malignancy via up-regulating CD44/STAT3 signaling pathway. Mol Med 2024;30:61. [PMID: 38760717 PMCID: PMC11100204 DOI: 10.1186/s10020-024-00827-6] [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: 02/18/2024] [Accepted: 05/04/2024] [Indexed: 05/19/2024] Open

Xu Z. CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024;397:2849-2876. [PMID: 37991544 DOI: 10.1007/s00210-023-02840-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/07/2023] [Indexed: 11/23/2023]

Yu C, Yuan H, Xu Y, Luo Y, Wu ZH, Zhong JJ, Xiao JH. Hyaluronan delays human amniotic epithelial stem cell senescence by regulating CD44 isoform switch to activate AKT/mTOR signals. Biomed Pharmacother 2024;170:116100. [PMID: 38159379 DOI: 10.1016/j.biopha.2023.116100] [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: 09/25/2023] [Revised: 12/19/2023] [Accepted: 12/26/2023] [Indexed: 01/03/2024] Open

Affiliation(s)

Chao Yu Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
Huan Yuan Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
Yan Xu Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
Yi Luo Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
Zuo-Hui Wu Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Department of Ultrasonography, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China.
Jian-Jiang Zhong Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Jian-Hui Xiao Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Department of Ultrasonography, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China.

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Kwon MJ. Role of epithelial splicing regulatory protein 1 in cancer progression. Cancer Cell Int 2023;23:331. [PMID: 38110955 PMCID: PMC10729575 DOI: 10.1186/s12935-023-03180-6] [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: 10/29/2023] [Accepted: 12/12/2023] [Indexed: 12/20/2023] Open

Tang Z, Xia Z, Wang X, Liu Y. The critical role of osteopontin (OPN) in fibrotic diseases. Cytokine Growth Factor Rev 2023;74:86-99. [PMID: 37648616 DOI: 10.1016/j.cytogfr.2023.08.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/22/2023] [Accepted: 08/22/2023] [Indexed: 09/01/2023]

Deng H, Gao J, Cao B, Qiu Z, Li T, Zhao R, Li H, Wei B. LncRNA CCAT2 promotes malignant progression of metastatic gastric cancer through regulating CD44 alternative splicing. Cell Oncol (Dordr) 2023;46:1675-1690. [PMID: 37354353 DOI: 10.1007/s13402-023-00835-4] [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] [Accepted: 05/30/2023] [Indexed: 06/26/2023] Open

Abstract

OBJECTIVE

Gastric cancer (GC) is one of the most malignant tumors worldwide. Thus, it is necessary to explore the underlying mechanisms of GC progression and develop novel therapeutic regimens. Long non-coding RNAs (lncRNAs) have been demonstrated to be abnormally expressed and regulate the malignant behaviors of cancer cells. Our previous research demonstrated that lncRNA colon cancer-associated transcript 2 (CCAT2) has potential value for GC diagnosis and discrimination. However, the functional mechanisms of lncRNA CCAT2 in GC development remain to be explored.

METHODS

GC and normal adjacent tissues were collected to detect the expression of lncRNA CCAT2, ESRP1 and CD44 in clinical specimens and their clinical significance for GC patients. Cell counting kit-8, wound healing and transwell assays were conducted to investigate the malignant behaviors in vitro. The generation of nude mouse xenografts by subcutaneous, intraperitoneal and tail vein injection was performed to examine GC growth and metastasis in vivo. Co-immunoprecipitation, RNA-binding protein pull-down assay and fluorescence in situ hybridization were performed to reveal the binding relationships between ESRP1 and CD44.

RESULTS

In the present study, lncRNA CCAT2 was overexpressed in GC tissues compared to adjacent normal tissues and correlated with short survival time of patients. lncRNA CCAT2 promoted the proliferation, migration and invasion of GC cells. Its overexpression modulates alternative splicing of Cluster of differentiation 44 (CD44) variants and facilitates the conversion from the standard form to variable CD44 isoform 6 (CD44v6). Mechanistically, lncRNA CCAT2 upregulated CD44v6 expression by binding to epithelial splicing regulatory protein 1 (ESRP1), which subsequently mediates CD44 alternative splicing. The oncogenic role of the lncRNA CCAT2/ESRP1/CD44 axis in the promotion of malignant behaviors was verified by both in vivo and in vitro experiments.

CONCLUSIONS

Our findings identified a novel mechanism by which lncRNA CCAT2, as a type of protein-binding RNA, regulates alternative splicing of CD44 and promotes GC progression. This axis may become an effective target for clinical diagnosis and treatment.

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Yan Z, Hu X, Tang B, Deng F. Role of osteopontin in cancer development and treatment. Heliyon 2023;9:e21055. [PMID: 37867833 PMCID: PMC10587537 DOI: 10.1016/j.heliyon.2023.e21055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 10/06/2023] [Accepted: 10/13/2023] [Indexed: 10/24/2023] Open

Bei Y, He J, Dong X, Wang Y, Wang S, Guo W, Cai C, Xu Z, Wei J, Liu B, Zhang N, Shen P. Targeting CD44 Variant 5 with an Antibody-Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma. Cancer Res 2023;83:2405-2420. [PMID: 37205633 PMCID: PMC10345965 DOI: 10.1158/0008-5472.can-23-0510] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/06/2023] [Accepted: 05/15/2023] [Indexed: 05/21/2023]

Affiliation(s)

Yuncheng Bei Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, PR China
Jian He Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
Xuhui Dong State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China
Yuxin Wang State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China
Sijie Wang State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China
Wan Guo State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China
Chengjie Cai State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China
Zhiye Xu Department of Clinical Laboratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
Jia Wei The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, PR China
Baorui Liu The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, PR China
Nan Zhang Centre of Micro/Nano Manufacturing Technology (MNMT-Dublin), School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
Pingping Shen Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China Shenzhen Research Institute of Nanjing University, Shenzhen, PR China

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Nairuz T, Mahmud Z, Manik RK, Kabir Y. Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance. Stem Cell Rev Rep 2023:10.1007/s12015-023-10529-x. [PMID: 37129728 DOI: 10.1007/s12015-023-10529-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2023] [Indexed: 05/03/2023]

Varsha VK, Savita JK, Girish HC, Shyamala K. Role of hypoxia and epithelial-mesenchymal transition in the formation and maintenance of oral cancer stem cells in oral squamous cell carcinomas and metastatic lymph node: An immunohistochemical analysis. J Oral Maxillofac Pathol 2023;27:307-314. [PMID: 37854934 PMCID: PMC10581292 DOI: 10.4103/jomfp.jomfp_368_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/14/2022] [Accepted: 12/06/2022] [Indexed: 10/20/2023] Open

Wang Q, Li S, Xu C, Hua A, Wang C, Xiong Y, Deng Q, Chen X, Yang T, Wan J, Ding ZY, Zhang BX, Yang X, Li Z. A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism. Pharmacol Res 2023;190:106740. [PMID: 36958408 DOI: 10.1016/j.phrs.2023.106740] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/13/2023] [Accepted: 03/17/2023] [Indexed: 03/25/2023]

Affiliation(s)

Qiang Wang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Shiyou Li National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Chen Xu National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Ao Hua National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Chong Wang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Yuxuan Xiong National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Qingyuan Deng National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Xiang Chen National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Tian Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Jiangling Wan National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Ze-Yang Ding Hepatic Surgery Center and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China
Bi-Xiang Zhang Hepatic Surgery Center and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China
Xiangliang Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; GBA Research Innovation Institute for Nanotechnology, Guangdong, 510530, P. R. China; Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Zifu Li National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China; Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

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Ghasempour S, Freeman SA. The glycocalyx and immune evasion in cancer. FEBS J 2023;290:55-65. [PMID: 34665926 DOI: 10.1111/febs.16236] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/27/2021] [Accepted: 10/18/2021] [Indexed: 01/14/2023]

Spadea A, Pingrajai P, Tirella A. Hyaluronic Acid-Based Nanotechnologies for Delivery and Treatment. BIOMEDICAL APPLICATIONS AND TOXICITY OF NANOMATERIALS 2023:103-128. [DOI: 10.1007/978-981-19-7834-0_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]

Zhang L, Chen W, Liu S, Chen C. Targeting Breast Cancer Stem Cells. Int J Biol Sci 2023;19:552-570. [PMID: 36632469 PMCID: PMC9830502 DOI: 10.7150/ijbs.76187] [Citation(s) in RCA: 59] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 12/09/2022] [Indexed: 01/04/2023] Open

Affiliation(s)

Lu Zhang Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; State Key Laboratory of Genetic Engineering; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai paracrine Key Laboratory of Medical Epigenetics; Shanghai Key Laboratory of Radiation Oncology; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College; Fudan University, Shanghai 200032, China
Wenmin Chen Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming 650201, China.,3Kunming College of Life Sciences, the University of the Chinese Academy of Sciences, Kunming 650201, China
Suling Liu Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences; State Key Laboratory of Genetic Engineering; Cancer Institutes; Key Laboratory of Breast Cancer in Shanghai; The Shanghai paracrine Key Laboratory of Medical Epigenetics; Shanghai Key Laboratory of Radiation Oncology; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology; Shanghai Medical College; Fudan University, Shanghai 200032, China.,4Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 211166, China.,✉ Corresponding authors: Ceshi Chen, E-mail: or Suling Liu, E-mail:
Ceshi Chen Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming 650201, China.,5Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China.,6The Third Affiliated Hospital, Kunming Medical University, Kunming 650118, China.,✉ Corresponding authors: Ceshi Chen, E-mail: or Suling Liu, E-mail:

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Li M, Yan T, Wang M, Cai Y, Wei Y. Advances in Single-Cell Sequencing Technology and Its Applications in Triple-Negative Breast Cancer. BREAST CANCER (DOVE MEDICAL PRESS) 2022;14:465-474. [PMID: 36540278 PMCID: PMC9760048 DOI: 10.2147/bctt.s388534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 12/07/2022] [Indexed: 09/10/2024]

Nakajima T, Uehara T, Iwaya M, Matsuda K, Wada M, Nagaya T, Ehara T, Ota H. Osteopontin expression in the invasive front stroma of colorectal adenocarcinoma is associated with tumor budding and prognosis. Pathol Res Pract 2022;240:154190. [PMID: 36332325 DOI: 10.1016/j.prp.2022.154190] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 10/23/2022] [Accepted: 10/25/2022] [Indexed: 11/06/2022]

Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression. J Mol Med (Berl) 2022;100:1539-1556. [PMID: 36163376 DOI: 10.1007/s00109-022-02257-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/31/2022] [Accepted: 09/12/2022] [Indexed: 12/14/2022]

CD44+/CD24- Expression as predictors of ovarian cancer chemoresistance: immunohistochemistry and flow cytometry study. J Egypt Natl Canc Inst 2022;34:44. [DOI: 10.1186/s43046-022-00143-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/23/2022] [Indexed: 12/24/2022] Open

Sihombing UHM, Andrijono, Purwoto G, Gandamihardja S, Harahap AR, Rustamadji P, Kekalih A, Widyawati R, Fuady DR. Expression of CD44+/CD24-, RAD6 and DDB2 on chemotherapy response in ovarian Cancer: A prospective flow cytometry study. Gynecol Oncol Rep 2022;42:101005. [PMID: 35707599 PMCID: PMC9189034 DOI: 10.1016/j.gore.2022.101005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 12/24/2022] Open

Abstract

•

Dear editor of Gynecologic Oncology Reports, these are the research highlights:

•

CD44⁺/CD24^- overexpression in blood circulation is associated with ovarian cancer chemoresistance.

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RAD6 overexpression in blood circulation is associated with ovarian cancer chemoresistance.

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CD44⁺/CD24^- expression in blood circulation is a good predictor of ovarian cancer chemoresistance.

Backgrounds

Ovarian cancer is the 8th deadliest common cancer in women around the world. Almost all ovarian cancer patients would experience chemoresistance, recurrence, and poor prognosis after cytoreductive surgery and platinum-based chemotherapy. Chemoresistant cancer cells have characteristic expressions of cancer stem cell proteins (CSCs) CD44⁺/CD24^-, RAD6 and DDB2. The increased expression of CD44⁺/CD24^-, RAD6, and decreased DDB2 are believed to be associated with chemoresistance, recurrence, and poor prognosis of the disease. Thus, this study’s objective is to analyze the correlation between the expression of CD44⁺/CD24^-, RAD6 and DDB2 with ovarian cancer chemoresistance.

Materials and methods

This study was conducted with a prospective cohort of 64 patients who is divided into two groups (32 patients in each group) at the Obstetrics-gynecology and pathology department of Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital. All suspected ovarian cancer patients underwent cytoreductive debulking and histopathological examination. Chemotherapy was given for six series followed by six months of observation. After the observation, we determined the therapy’s response with the RECIST Criteria (Response Criteria in Solid Tumors) and then classified the results into chemoresistant or chemosensitive groups. Flow cytometry blood tests were then performed to examine the expression of CD44⁺/CD24^-, RAD6 and DDB2.

Results

There was a significant relationship between increased levels of CD44⁺/CD24^-, and RAD6 (p < 0.05) levels with the chemoresistance of ovarian cancer. The logistic regression test showed that the CD44⁺/CD24^– was better marker.

Conclusions

These results indicate that CD44⁺/CD24 and RAD6 expressions are significantly associated with ovarian cancer chemoresistance, and CD44⁺/CD24^- is the better marker to predict ovarian cancer chemoresistance.

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Gao F, Zhang G, Liu Y, He Y, Sheng Y, Sun X, Du Y, Yang C. Activation of CD44 signaling in leader cells induced by tumor-associated macrophages drives collective detachment in luminal breast carcinomas. Cell Death Dis 2022;13:540. [PMID: 35680853 PMCID: PMC9184589 DOI: 10.1038/s41419-022-04986-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 05/17/2022] [Accepted: 05/30/2022] [Indexed: 01/21/2023]

Guo L, Ke H, Zhang H, Zou L, Yang Q, Lu X, Zhao L, Jiao B. TDP43 promotes stemness of breast cancer stem cells through CD44 variant splicing isoforms. Cell Death Dis 2022;13:428. [PMID: 35504883 PMCID: PMC9065105 DOI: 10.1038/s41419-022-04867-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 04/13/2022] [Accepted: 04/19/2022] [Indexed: 12/14/2022]

Affiliation(s)

Lu Guo grid.9227.e0000000119573309State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 Yunnan China ,2grid.410726.60000 0004 1797 8419Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650201 China
Hao Ke grid.260463.50000 0001 2182 8825Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang, 330031 Jiangxi China
Honglei Zhang grid.440773.30000 0000 9342 2456Center for Scientific Research, Yunnan University of Chinese Medicine, Kunming, 650500 Yunnan China
Li Zou grid.9227.e0000000119573309State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 Yunnan China
Qin Yang grid.9227.e0000000119573309State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 Yunnan China
Xuemei Lu grid.9227.e0000000119573309State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 Yunnan China ,5grid.9227.e0000000119573309KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan China
Limin Zhao grid.260463.50000 0001 2182 8825Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang, 330031 Jiangxi China
Baowei Jiao grid.9227.e0000000119573309State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201 Yunnan China ,5grid.9227.e0000000119573309KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan China

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Evaluation of Immunoregulatory Biomarkers on Plasma Small Extracellular Vesicles for Disease Progression and Early Therapeutic Response in Head and Neck Cancer. Cells 2022;11:cells11050902. [PMID: 35269524 PMCID: PMC8909035 DOI: 10.3390/cells11050902] [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: 02/11/2022] [Revised: 02/28/2022] [Accepted: 03/03/2022] [Indexed: 12/24/2022] Open

The molecular underpinning of geminin-overexpressing triple-negative breast cancer cells homing specifically to lungs. Cancer Gene Ther 2022;29:304-325. [PMID: 33723406 DOI: 10.1038/s41417-021-00311-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 01/23/2021] [Accepted: 02/12/2021] [Indexed: 01/31/2023]

Abstract

Triple-negative breast cancer (TNBCs) display lung metastasis tropism. However, the mechanisms underlying this organ-specific pattern remains to be elucidated. We sought to evaluate the utility of blocking extravasation to prevent lung metastasis. To identify potential geminin overexpression-controlled genetic drivers that promote TNBC tumor homing to lungs, we used the differential/suppression subtractive chain (D/SSC) technique. A geminin overexpression-induced lung metastasis gene signature consists of 24 genes was discovered. We validated overexpression of five of these genes (LGR5, HAS2, CDH11, NCAM2, and DSC2) in worsening lung metastasis-free survival in TNBC patients. Our data demonstrate that LGR5-induced β-catenin signaling and stemness in TNBC cells are geminin-overexpression dependent. They also demonstrate for the first-time expression of RSPO2 in mouse lung tissue only and exacerbation of its secretion in the circulation of mice that develop geminin overexpressing/LGR5⁺-TNBC lung metastasis. We identified a novel extravasation receptor complex, consists of CDH11, CD44v6, c-Met, and AXL on geminin overexpressing/LGR5⁺-TNBC lung metastatic precursors, inhibition of any of its receptors prevented geminin overexpressing/LGR5⁺-TNBC lung metastasis. Overall, we propose that geminin overexpression in normal mammary epithelial (HME) cells promotes the generation of TNBC metastatic precursors that home specifically to lungs by upregulating LGR5 expression and promoting stemness, intravasation, and extravasation in these precursors. Circulating levels of RSPO2 and OPN can be diagnostic biomarkers to improve risk stratification of metastatic TNBC to lungs, as well as identifying patients who may benefit from therapy targeting geminin alone or in combination with any member of the newly discovered extravasation receptor complex to minimize TNBC lung metastasis.

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Naz F, Shi M, Sajid S, Yang Z, Yu C. Cancer stem cells: a major culprit of intra-tumor heterogeneity. Am J Cancer Res 2021;11:5782-5811. [PMID: 35018226 PMCID: PMC8727794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 08/25/2021] [Indexed: 06/14/2023] Open

Xiong Q, Wang M, Liu J, Lin CY. Breast Cancer Cells Metastasize to the Tissue-Engineered Premetastatic Niche by Using an Osteoid-Formed Polycaprolactone/Nanohydroxyapatite Scaffold. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2021;2021:9354202. [PMID: 34938359 PMCID: PMC8687766 DOI: 10.1155/2021/9354202] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/23/2021] [Indexed: 11/21/2022]

Abstract

It has been deemed that the premetastatic niche (PMN) plays a critical role in facilitating bone metastasis of breast cancer cells. Tissue engineering scaffolds provide an advantageous environment to promote osteogenesis that may mimic the bony premetastatic niches (BPMNs). In this study, human mesenchymal stem cells (hMSCs) were seeded onto designed polycaprolactone/nanohydroxyapatite (PCL-nHA) scaffolds for osteogenic differentiation. Subsequently, a coculture system was used to establish the tissue-engineered BPMNs by culturing breast cancer cells, hMSCs, and osteoid-formed PCL-nHA scaffolds. Afterwards, a migration assay was used to investigate the recruitment of MDA-MB-231, MCF-7, and MDA-MB-453 cells to the BPMNs' supernatants. The cancer stem cell (CSC) properties of these migrated cells were investigated by flow cytometry. Our results showed that the mRNA expression levels of alkaline phosphatase (ALP), Osterix, runt-related transcription factor 2 (Runx2), and collagen type I alpha 1 (COL1A1) on the PCL-nHA scaffolds were dramatically increased compared to the PCL scaffolds on days 11, 18, and 32. The expression of CXCL12 in these BPMNs was increased gradually over coculturing time, and it may be a feasible marker for BPMNs. Furthermore, migration analysis results showed that the higher maturation of BPMNs collectively contributed to the creation of a more favorable niched site for the cancerous invasion. The subpopulation of breast cancer stem cells (BCSCs) was more likely to migrate to fertile BPMNs. The proportion of BCSCs in metastatic MDA-MB-231, MCF-7, and MDA-MB-453 cells were increased by approximately 63.47%, 149.48%, and 127.60%. The current study demonstrated that a designed tissue engineering scaffold can provide a novel method to create a bone-mimicking environment that serves as a useable platform to recapitulate the BPMNs and help interrogate the scheme of bone metastasis by breast cancer.

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Ebrahimie E, Rahimirad S, Tahsili M, Mohammadi-Dehcheshmeh M. Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis. World J Stem Cells 2021;13:1394-1416. [PMID: 34786151 PMCID: PMC8567453 DOI: 10.4252/wjsc.v13.i10.1394] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 06/21/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open

Liu Y, Zhang P, Wu Q, Fang H, Wang Y, Xiao Y, Cong M, Wang T, He Y, Ma C, Tian P, Liang Y, Qin LX, Yang Q, Yang Q, Liao L, Hu G. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63. Nat Commun 2021;12:5232. [PMID: 34475402 PMCID: PMC8413371 DOI: 10.1038/s41467-021-25552-0] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 08/17/2021] [Indexed: 12/23/2022] Open

Affiliation(s)

Yingjie Liu CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.,Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, Shanghai, China
Peiyuan Zhang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Qiuyao Wu CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Houqin Fang Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China
Yuan Wang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Yansen Xiao CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Min Cong CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Tingting Wang Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China
Yunfei He CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Chengxin Ma CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Pu Tian CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Yajun Liang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Lun-Xiu Qin Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China
Qingcheng Yang Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
Qifeng Yang Department of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, China
Lujian Liao Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China
Guohong Hu CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. .,Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, Shanghai, China.

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Qian J, LeSavage BL, Hubka KM, Ma C, Natarajan S, Eggold JT, Xiao Y, Fuh KC, Krishnan V, Enejder A, Heilshorn SC, Dorigo O, Rankin EB. Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling. J Clin Invest 2021;131:e146186. [PMID: 34396988 DOI: 10.1172/jci146186] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 06/25/2021] [Indexed: 12/28/2022] Open

Manupati K, Yeeravalli R, Kaushik K, Singh D, Mehra B, Gangane N, Gupta A, Goswami K, Das A. Activation of CD44-Lipoprotein lipase axis in breast cancer stem cells promotes tumorigenesis. Biochim Biophys Acta Mol Basis Dis 2021;1867:166228. [PMID: 34311079 DOI: 10.1016/j.bbadis.2021.166228] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 06/25/2021] [Accepted: 07/20/2021] [Indexed: 01/16/2023]

Nakhjavani M, Smith E, Palethorpe HM, Tomita Y, Yeo K, Price TJ, Townsend AR, Hardingham JE. Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models. Pharmaceuticals (Basel) 2021;14:ph14070633. [PMID: 34208799 PMCID: PMC8308773 DOI: 10.3390/ph14070633] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 06/23/2021] [Accepted: 06/23/2021] [Indexed: 12/26/2022] Open

Affiliation(s)

Maryam Nakhjavani Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; (M.N.); (Y.T.); (K.Y.); (J.E.H.) Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.)
Eric Smith Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; (M.N.); (Y.T.); (K.Y.); (J.E.H.) Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.) Correspondence: ; Tel.: +61-8-8222-6142
Helen M. Palethorpe Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia;
Yoko Tomita Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; (M.N.); (Y.T.); (K.Y.); (J.E.H.) Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.) Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia
Kenny Yeo Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; (M.N.); (Y.T.); (K.Y.); (J.E.H.) Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.)
Tim J. Price Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.) Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia
Amanda R. Townsend Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.) Oncology Unit, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia
Jennifer E. Hardingham Molecular Oncology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA 5011, Australia; (M.N.); (Y.T.); (K.Y.); (J.E.H.) Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; (T.J.P.); (A.R.T.)

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Gu P, Sun M, Li L, Yang Y, Jiang Z, Ge Y, Wang W, Mu W, Wang H. Breast Tumor-Derived Exosomal MicroRNA-200b-3p Promotes Specific Organ Metastasis Through Regulating CCL2 Expression in Lung Epithelial Cells. Front Cell Dev Biol 2021;9:657158. [PMID: 34249913 PMCID: PMC8264457 DOI: 10.3389/fcell.2021.657158] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 05/25/2021] [Indexed: 01/20/2023] Open

Affiliation(s)

Pengfei Gu State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Mayu Sun State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai, China
Lei Li Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yang Yang State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai, China
Zheshun Jiang State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yang Ge State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wenbo Wang Department of Oncology, Shanghai Tenths People’s Hospital, School of Medicine, Tongji University, Shanghai, China
Wei Mu State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hui Wang State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai, China

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Batsché E, Yi J, Mauger O, Kornobis E, Hopkins B, Hanmer-Lloyd C, Muchardt C. CD44 alternative splicing senses intragenic DNA methylation in tumors via direct and indirect mechanisms. Nucleic Acids Res 2021;49:6213-6237. [PMID: 34086943 PMCID: PMC8216461 DOI: 10.1093/nar/gkab437] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/30/2021] [Accepted: 05/05/2021] [Indexed: 02/07/2023] Open

Fontanella RA, Sideri S, Di Stefano C, Catizone A, Di Agostino S, Angelini DF, Guerrera G, Battistini L, Battafarano G, Del Fattore A, Campese AF, Padula F, De Cesaris P, Filippini A, Riccioli A. CD44v8-10 is a marker for malignant traits and a potential driver of bone metastasis in a subpopulation of prostate cancer cells. Cancer Biol Med 2021;18:j.issn.2095-3941.2020.0495. [PMID: 34018387 PMCID: PMC8330537 DOI: 10.20892/j.issn.2095-3941.2020.0495] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 03/08/2021] [Indexed: 12/14/2022] Open

Abstract

OBJECTIVE

Bone metastasis is a clinically important outcome of prostate carcinoma (PC). We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell line. These cells, originated from the spontaneous conversion of a CD44-negative subpopulation, stably express the CD44v8-10 isoform (CD44v8-10pos) and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44v8-10 silencing.

METHODS

Flow cytometry, enzyme-linked immunoassay, immunofluorescence, and Western blot were used for phenotypic and immunologic characterization. Real-time quantitative polymerase chain reaction and functional assays were used to assess osteomimicry.

RESULTS

Analysis of epithelial-mesenchymal transition markers showed that CD44v8-10pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry, acquiring bone cell phenotypic and behavioral traits. Use of specific siRNA evidenced the ability of CD44v8-10 variant to confer osteomimetic features, hence the potential to form bone-specific metastasis. Moreover, the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a tumor. Here we report that CD44v8-10pos cells express programmed death ligand 1, a negative regulator of anticancer immunity, and secrete exceptionally high amounts of interleukin-6, favoring osteoclastogenesis and immunosuppression in bone microenvironment. Notably, we identified a novel pathway activated by CD44v8-10, involving tafazzin (TAZ) and likely the Wnt/TAZ axis, known to play a role in upregulating osteomimetic genes.

CONCLUSIONS

CD44v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone. A novel link between TAZ and CD44v8-10 is also shown.

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Affiliation(s)

Rosaria A. Fontanella Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy
Silvia Sideri Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy
Chiara Di Stefano Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy
Angiolina Catizone Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy
Silvia Di Agostino Department of Health Sciences School of Medicine – “Magna Graecia” University of Catanzaro, Catanzaro 88100, Italy
Daniela F. Angelini IRCCS Fondazione Santa Lucia, Rome 00143, Italy
Gisella Guerrera IRCCS Fondazione Santa Lucia, Rome 00143, Italy
Luca Battistini IRCCS Fondazione Santa Lucia, Rome 00143, Italy
Giulia Battafarano Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Rome 00146, Italy
Andrea Del Fattore Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Rome 00146, Italy
Antonio Francesco Campese Department of Molecular Medicine, Sapienza University, Rome 00161, Italy
Fabrizio Padula Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy
Paola De Cesaris Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila 67100, Italy
Antonio Filippini Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy
Anna Riccioli Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University, Rome 00161, Italy

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Song Z, Chen W, Athavale D, Ge X, Desert R, Das S, Han H, Nieto N. Osteopontin Takes Center Stage in Chronic Liver Disease. Hepatology 2021;73:1594-1608. [PMID: 32986864 PMCID: PMC8106357 DOI: 10.1002/hep.31582] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/25/2020] [Accepted: 09/09/2020] [Indexed: 12/13/2022]

Yoshida GJ, Saya H. Molecular pathology underlying the robustness of cancer stem cells. Regen Ther 2021;17:38-50. [PMID: 33869685 PMCID: PMC8024885 DOI: 10.1016/j.reth.2021.02.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 02/08/2021] [Indexed: 02/06/2023] Open

Abstract

Intratumoral heterogeneity is tightly associated with the failure of anticancer treatment modalities including conventional chemotherapy, radiation therapy, and molecularly targeted therapy. Such heterogeneity is generated in an evolutionary manner not only as a result of genetic alterations but also by the presence of cancer stem cells (CSCs). CSCs are proposed to exist at the top of a tumor cell hierarchy and are undifferentiated tumor cells that manifest enhanced tumorigenic and metastatic potential, self-renewal capacity, and therapeutic resistance. Properties that contribute to the robustness of CSCs include the abilities to withstand redox stress, to rapidly repair damaged DNA, to adapt to a hyperinflammatory or hyponutritious tumor microenvironment, and to expel anticancer drugs by the action of ATP-binding cassette transporters as well as plasticity with regard to the transition between dormant CSC and transit-amplifying progenitor cell phenotypes. In addition, CSCs manifest the phenomenon of metabolic reprogramming, which is essential for maintenance of their self-renewal potential and their ability to adapt to changes in the tumor microenvironment. Elucidation of the molecular underpinnings of these biological features of CSCs is key to the development of novel anticancer therapies. In this review, we highlight the pathological relevance of CSCs in terms of their hallmarks and identification, the properties of their niche—both in primary tumors and at potential sites of metastasis—and their resistance to oxidative stress dependent on system xc (−).

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Intratumoral heterogeneity driven by CSCs is responsible for therapeutic resistance.

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CTCs survive in the distant organs and achieve colonization, causing metastasis.

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E/M hybrid cancer cells due to partial EMT exhibit the highest metastatic potential.

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The CSC niche regulates stemness in metastatic disease as well as in primary tumor.

•

Activation of system xc(-) by CD44 variant in CSCs is a promising therapeutic target.

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Xiao Y, Cong M, Li J, He D, Wu Q, Tian P, Wang Y, Yang S, Liang C, Liang Y, Wen J, Liu Y, Luo W, Lv X, He Y, Cheng DD, Zhou T, Zhao W, Zhang P, Zhang X, Xiao Y, Qian Y, Wang H, Gao Q, Yang QC, Yang Q, Hu G. Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell 2021;39:423-437.e7. [PMID: 33450198 DOI: 10.1016/j.ccell.2020.12.012] [Citation(s) in RCA: 327] [Impact Index Per Article: 81.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 11/08/2020] [Accepted: 12/10/2020] [Indexed: 12/30/2022]

Affiliation(s)

Yansen Xiao CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Min Cong CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
Jiatao Li CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Dasa He CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Qiuyao Wu CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Pu Tian CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yuan Wang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Shuaixi Yang Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
Chenxi Liang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yajun Liang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Jili Wen CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yingjie Liu CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Wenqian Luo CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Xianzhe Lv CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yunfei He CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Dong-Dong Cheng Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
Tianhao Zhou Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
Wenjing Zhao Department of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, 250012, China
Peiyuan Zhang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Xue Zhang CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Yichuan Xiao CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Youcun Qian CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
Hongxia Wang Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China
Qiang Gao Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, 200032, China
Qing-Cheng Yang Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
Qifeng Yang Department of Breast Surgery, Qilu Hospital of Shandong University, Ji'nan, 250012, China
Guohong Hu CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

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Guo Q, Liu Y, He Y, Du Y, Zhang G, Yang C, Gao F. CD44 activation state regulated by the CD44v10 isoform determines breast cancer proliferation. Oncol Rep 2021;45:7. [PMID: 33649828 PMCID: PMC7876991 DOI: 10.3892/or.2021.7958] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 01/14/2021] [Indexed: 12/27/2022] Open

Xu C, Gu Z, Liu J, Lin X, Wang C, Li J, Fu Y, Cheng X, Zhuang Z. Adenosquamous carcinoma of the breast: a population-based study. Breast Cancer 2021;28:848-858. [PMID: 33580464 PMCID: PMC8213591 DOI: 10.1007/s12282-021-01222-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 01/21/2021] [Indexed: 11/29/2022]

Aramini B, Masciale V, Grisendi G, Banchelli F, D'Amico R, Maiorana A, Morandi U, Dominici M, Haider KH. Cancer stem cells and macrophages: molecular connections and future perspectives against cancer. Oncotarget 2021;12:230-250. [PMID: 33613850 PMCID: PMC7869576 DOI: 10.18632/oncotarget.27870] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 01/07/2021] [Indexed: 12/12/2022] Open

Nimmakayala RK, Leon F, Rachagani S, Rauth S, Nallasamy P, Marimuthu S, Shailendra GK, Chhonker YS, Chugh S, Chirravuri R, Gupta R, Mallya K, Prajapati DR, Lele SM, C Caffrey T, L Grem J, Grandgenett PM, Hollingsworth MA, Murry DJ, Batra SK, Ponnusamy MP. Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma. Oncogene 2021;40:215-231. [PMID: 33110235 PMCID: PMC10041665 DOI: 10.1038/s41388-020-01518-2] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/02/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023]

Abstract

Pancreatic ductal adenocarcinoma (PDAC) metastasizes to distant organs, which is the primary cause of mortality; however, specific features mediating organ-specific metastasis remain unexplored. Emerging evidence demonstrates that cancer stem cells (CSCs) and cellular metabolism play a pivotal role in metastasis. Here we investigated the role of distinct subtypes of pancreatic CSCs and their metabolomic signatures in organ-specific metastatic colonization. We found that PDAC consists of ALDH+/CD133+ and drug-resistant (MDR1+) subtypes of CSCs with specific metabolic and stemness signatures. Human PDAC tissues with gemcitabine treatment, autochthonous mouse tumors from Kras^G12D; Pdx1-Cre (KC) and Kras^G12D; Trp53^R172H; Pdx-1 Cre (KPC) mice, and KPC- Liver/Lung metastatic cells were used to evaluate the CSC, EMT (epithelial-to-mesenchymal transition), and metabolic profiles. A strong association was observed between distinct CSC subtypes and organ-specific colonization. The liver metastasis showed drug-resistant CSC- and EMT-like phenotype with aerobic glycolysis and fatty acid β-oxidation-mediated oxidative (glyco-oxidative) metabolism. On the contrary, lung metastasis displayed ALDH+/CD133+ and MET-like phenotype with oxidative metabolism. These results were obtained by evaluating FACS-based side population (SP), autofluorescence (AF+) and Alde-red assays for CSCs, and Seahorse-based oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and fatty acid β-oxidation (FAO)-mediated OCR assays for metabolic features along with specific gene signatures. Further, we developed in vitro human liver and lung PDAC metastasis models by using a combination of liver or lung decellularized scaffolds, a co-culture, and a sphere culture methods. PDAC cells grown in the liver-mimicking model showed the enrichment of MDR1+ and CPT1A+ populations, whereas the PDAC cells grown in the lung-mimicking environment showed the enrichment of ALDH+/CD133+ populations. In addition, we observed significantly elevated expression of ALDH1 in lung metastasis and MDR1/LDH-A expression in liver metastasis compared to human primary PDAC tumors. Our studies elucidate that distinct CSCs adapt unique metabolic signatures for organotropic metastasis, which will pave the way for the development of targeted therapy for PDAC metastasis.

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Affiliation(s)

Rama Krishna Nimmakayala Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Frank Leon Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Satyanarayana Rachagani Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Sanchita Rauth Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Palanisamy Nallasamy Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Saravanakumar Marimuthu Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Gautam K Shailendra Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Yashpal S Chhonker Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, 986145 Nebraska Medical Center, Omaha, NE, 68198-6145, USA
Seema Chugh Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Ramakanth Chirravuri Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Rohitesh Gupta Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Kavita Mallya Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA
Dipakkumar R Prajapati Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
Subodh M Lele Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
Thomas C Caffrey Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
Jean L Grem Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
Paul M Grandgenett Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
Michael A Hollingsworth Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
Daryl J Murry Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, 986145 Nebraska Medical Center, Omaha, NE, 68198-6145, USA
Surinder K Batra Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA. .,Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Moorthy P Ponnusamy Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA. .,Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.

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Liang RB, Yu K, Wu JL, Liu JX, Lin Q, Li B, Zhang YQ, Ge QM, Li QY, Shu HY, Shao Y. Risk factors and their diagnostic values for ocular metastases in invasive ductal carcinoma. Cancer Med 2020;10:824-832. [PMID: 33336932 PMCID: PMC7897965 DOI: 10.1002/cam4.3656] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 11/04/2020] [Accepted: 11/13/2020] [Indexed: 12/13/2022] Open

Martincuks A, Li PC, Zhao Q, Zhang C, Li YJ, Yu H, Rodriguez-Rodriguez L. CD44 in Ovarian Cancer Progression and Therapy Resistance-A Critical Role for STAT3. Front Oncol 2020;10:589601. [PMID: 33335857 PMCID: PMC7736609 DOI: 10.3389/fonc.2020.589601] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/22/2020] [Indexed: 12/15/2022] Open

Bei Y, Cheng N, Chen T, Shu Y, Yang Y, Yang N, Zhou X, Liu B, Wei J, Liu Q, Zheng W, Zhang W, Su H, Zhu W, Ji J, Shen P. CDK5 Inhibition Abrogates TNBC Stem-Cell Property and Enhances Anti-PD-1 Therapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2020;7:2001417. [PMID: 33240752 PMCID: PMC7675186 DOI: 10.1002/advs.202001417] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 08/12/2020] [Indexed: 06/11/2023]

Affiliation(s)

Yuncheng Bei State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Nan Cheng State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Ting Chen State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China Laura and Isaac Perlmutter Cancer CenterNew York University Langone Medical CenterNew YorkNYUSA
Yuxin Shu State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Ye Yang State Key Laboratory Cultivation Base for TCM Quality and EfficacyNanjing University of Chinese MedicineNanjing210023P. R. China
Nanfei Yang State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Xinyu Zhou State Key Laboratory of Protein and Plant Gene ResearchCollege of Life SciencesPeking UniversityBeijing100871P. R. China
Baorui Liu The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
Jia Wei The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
Qin Liu The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
Wei Zheng State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Wenlong Zhang State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Huifang Su State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China
Wei‐Guo Zhu Guangdong Key Laboratory of Genome Instability and Human DiseaseShenzhen University Carson Cancer CenterDepartment of Biochemistry and Molecular BiologyShenzhen University School of MedicineShenzhen518060P. R. China
Jianguo Ji State Key Laboratory of Protein and Plant Gene ResearchCollege of Life SciencesPeking UniversityBeijing100871P. R. China
Pingping Shen State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer CenterNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210046P. R. China Guangdong Key Laboratory of Genome Instability and Human DiseaseShenzhen University Carson Cancer CenterDepartment of Biochemistry and Molecular BiologyShenzhen University School of MedicineShenzhen518060P. R. China

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Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun AR, Yevsa T, Fricke S, Kossatz-Boehlert U. Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front Immunol 2020;11:1280. [PMID: 32849491 PMCID: PMC7426526 DOI: 10.3389/fimmu.2020.01280] [Citation(s) in RCA: 544] [Impact Index Per Article: 108.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open

Abstract

The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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