EV-mediated asymmetrical crosstalk between CAFs and cancer cells in the tumor microenvironment

Tumor is a complex tissue composed of both genetically transformed cancer cells and the cells of the tumor microenvironment, including connective cells, immune cells, and endothelial cells that actively contribute to the maintenance of the tumor and, consequently, to its progression. As for any other tissue, the communication between cells of the tumor microenvironment plays an essential role in determining the architecture and physiology of the tumor tissue. This intercellular communication is classically mediated by soluble factors (such as cytokines and growth factors) but it has been shown that the extracellular vesicle (EV) trafficking may also contribute to tumor growth and progression. In this paper, we discuss the EV-mediated transfer of proteins between cancer cells and cancer-associated fibroblasts (CAFs) in an attempt to propose an interpretation of the relationships between these two cell types within the tumor microenvironment. In particular, we propose that this type of crosstalk between cancer cells and CAFs is asymmetrical: on the one hand, cancer cells secrete signaling protein-bearing exosomes that induce the trans-differentiation of neighboring fibroblasts into CAFs; on the other hand, CAFs transfer biomass to cancer cells through ectosome trafficking, thus supporting cancer cell proliferation.