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

Cells

Shimrit Avraham¹  Dvir Shechter¹  Yuval Shaked¹  Elad Prinz¹  Abhishek Mukherjee²  Haguy Wolfenson²  Michal Harel³  Tamar Geiger³  David Loven⁴  LeonelM. Sagredo⁵  Veronique Orian-Rousseau⁵ 

[1] Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa 3525433, Israel;Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa 31096, Israel;Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel;Department of Oncology, Ha’Emek Medical Center, Afula 1834111, Israel;Karlsruhe Institute of Technology, Institute of Biological and Chemical Systems–Functional Molecular Systems (IBCS-FMS), 76021 Karlsruhe, Germany;

关键词: chemotherapy;    breast cancer;    adhesion;    metastasis;    CD44;    extracellular vesicles;   

DOI  :  10.3390/cells9102269

来源: DOAJ

【 摘 要 】

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. We also demonstrated that breast cancer patients treated with paclitaxel chemotherapy exhibited increased CD44-expressing TMPs. Overall, our study provides further insights into the role of TMPs in promoting metastasis, an effect which is augmented when tumor cells are exposed to chemotherapy.

【 授权许可】

Unknown