Fig. 1.

Cancer cell-derived EVs modify the characters of cancer surrounding microenvironment. Several kinds of cell types, such as cancer cells, fibroblasts, immune cells, endothelial cells, epithelial cells, and mesenchymal stem cells, comprise unique microenvironment for cancer progression. Cancer cells utilize EVs to modify surrounding cells within tumor microenvironment. Cancer-derived EVs have multiple functions that depend on component molecules of EVs. To induce cancer-associated fibroblast (CaF)-like phenotypes in cancer surrounding fibroblasts and mesenchymal stem cells, cancer cells secrete EVs and transfer growth factors and microRNAs (miRNAs), including transforming growth factor-beta (TGF-β) and miR-155, respectively. To escape from immune surveillance, cancer cells transfer several types of immunoregulatory molecules into immune cells. However, these cancer-derived EVs also stimulate cancer immunity to kill tumor cells because tumor antigens were packaged in EVs and stimulated cancer immunity. Cancer-derived EVs also contain angiogenic proteins and miRNAs that promote migration and proangiogenic activity of endothelial cells. In addition, miR-105 and miR-181c in EVs are capable of rupturing the vascular system to increase the permeability that supports cancer metastasis. Cancer-derived EVs confer malignant phenotypes in other cancer cells and epithelial cells by transferring oncogenic proteins and miRNAs, such as EGFRvIII, miR-200, and tissue transglutaminase (tTG). Taken together, cancer cells “dictate” the characters of their surrounding stromal cells and create a convenient microenvironment to support cancer progression via EVs