Fig. 2.

The functional role of non-tumoral cell-derived EVs in cancer initiation and progression. Non-tumoral cells utilize EVs to affect cancer initiation and progression. Cancer-associated fibroblasts secrete EVs and affect invasion, proliferation, chemoresistance, and metabolic properties of cancer cells by transferring CD81, miR-21, miR-409, and metabolites. Macrophage-derived EVs contain miR-223, which stimulates the invasive activity of cancer cells. Monocytes transfer miR-155 to neuroblastoma via EVs and induce chemoresistance in neuroblastoma. “Non-educated” mesenchymal stem cells (MSCs) by cancer cells secrete EVs containing miR-16 to suppress tumor growth and angiogenesis. However, interestingly, “educated” MSCs by cancer cells enable to secrete EVs that contain tumor promotive proteins such as plakoglobin and CCL2. MSC-derived EVs also transfer miR-23b, which induce dormant state of cancer cells to survive in a quiescent state while waiting for the appropriate environmental conditions to begin proliferation again. Non-aberrant epithelial cells secreted EVs to transfer miR-143 into cancer cells and suppress tumor growth