The role of miRNAs in the extracellular vesicle-mediated interplay between breast tumor cells and cancer-associated fibroblasts

Abstract

The tumor microenvironment (TME) of breast cancer (BC) is depicted as an immunosuppressive dwelling that comprises a myriad of cell types embedded in the extracellular matrix. As one of the most abundant cell populations within the TME, cancer-associated fibroblasts (CAFs) play indispensable roles in increasing cancer aggressiveness and promoting resistance to standard-of-care therapies. Extracellular vesicles (EVs) represent a diverse array of biological nanoparticles, encompassing exosomes, microvesicles, and apoptotic bodies. In recent years, these cell-derived membranous structures have raised great interest as they can encapsulate numerous types of cellular cargo, such as proteins, lipids, and miRNAs. By transmitting bioactive content to recipient cells, EVs play pivotal roles in intercellular communication between CAFs and tumor cells. EVs secreted from tumor cells typically activate resident fibroblasts to acquire a myofibroblastic phenotype, while EVs diffused by CAFs, in turn, substantially increase the progression of BC. This review summarizes the latest findings to highlight the functional role of EV cargo, especially miRNAs, in the regulatory network. A better understanding of the EV-mediated cell-cell interactions is crucial to achieving effective treatment in patients with BC.