(28ah) Role of Extracellular Vesicles in Maintaining Stemness in Breast Cancer Metastasis

Most cancer deaths are caused by secondary metastasized tumors initiated by circulating tumor cells (CTCs). These cells are in a dynamic microenvironment where fluid shear stress (FSS) typically impacts the survival of cells in circulation, suggesting there is an overlap in the populations of CTCs and more robust cancer stem cells (CSCs). It has not been definitively established how stemness traits are commuted from CSCs to non-CSCs. Cell communications are profoundly impacted by the microenvironment, including FSS. A notable means of cell-cell communication is facilitated through extracellular vesicles (EVs). EVs are capable of carrying genetic cargo such as DNA, RNA, miRNA and proteins that are interpreted by recipient cells and influence their behavior. The quality and contents of EVs have been shown to be affected by the cells producing them, as well as the culture environment and stresses the producing cells sustain. This work demonstrates the effects of FSS on EV production as well as their contents, including miR-21 which has been shown to promote metastatic progression and chemotherapeutic resistance. Further, we have analyzed the impact of CSC-derived EVs (MDA-MB-231) on non-CSCs (MCF7) with focus on the epithelial-to-mesenchymal transition (EMT) by way of the Hippo pathway. These findings indicate that stemness markers are influenced by EVs in breast cancer and directly correlate to the ability to undergo the EMT in breast cancer cells.