Also, the transference of an aggressive behavior that is mediated by sEVs might also involve the crosstalk between cancer cells and non-cancer cells within the tumor microenvironment (TME).53 EVs are known to activate the TGF-β signaling in non-cancer cells, inducing fibroblast activation18,19,30 and immunosuppression.20,54 Therefore, cancer cell-sEVs may not only activate, but also accelerate the co-option of a pro-metastatic TME by enhancing the activity of TGF-β and other growth factors by targeting non-cancer cells. The gene discussed is TGFB1; the disease is cancer.