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Breast Cancer-Derived Microparticles Reduce Cancer Cell Adhesion, an Effect Augmented by Chemotherapy

Shechter, Dvir; Harel, Michal; Mukherjee, Abhishek; Sagredo, Leonel M.; Loven, David; Prinz, Elad; Avraham, Shimrit; Orian-Rousseau, Veronique; Geiger, Tamar; Shaked, Yuval; Wolfenson, Haguy

Abstract:
Tumor cell heterogeneity is primarily dictated by mutational changes, sometimes leading to clones that undergo a metastatic switch. However, little is known about tumor heterogeneity following chemotherapy perturbation. Here we studied the possible involvement of tumor-derived extracellular vesicles, often referred to as tumor-derived microparticles (TMPs), as mediators of the metastatic switch in the tumor microenvironment by hindering cell adhesion properties. Specifically, we show that highly metastatic or chemotherapy-treated breast cancer cells shed an increased number of TMPs compared to their respective controls. We found that these TMPs substantially reduce cell adhesion and disrupt actin filament structure, therefore increasing their biomechanical force pace, further implicating tumor cell dissemination as part of the metastatic cascade. Our results demonstrate that these pro-metastatic effects are mediated in part by CD44 which is highly expressed in TMPs obtained from highly metastatic cells or cells exposed to chemotherapy when compared to cells with low metastatic potential. Consequently, when we inhibited CD44 expression on TMPs by a pharmacological or a genetic approach, increased tumor cell adhesion and re-organized actin filament structure were observed. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000127081
Veröffentlicht am 02.12.2020
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2073-4409
KITopen-ID: 1000127081
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Cells
Verlag MDPI
Band 9
Heft 10
Seiten 2269
Vorab online veröffentlicht am 10.10.2020
Schlagwörter chemotherapy; breast cancer; adhesion; metastasis; CD44; extracellular vesicles
Nachgewiesen in Dimensions
Web of Science
Scopus
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