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Figure 3. Illustrative examples of EV-GPCR oncomodulation. (A) MV3 melanoma cell-derived EVs activate primary neutrophils to adopt a pro-tumor/N2-phenotype by increasing the expression of chemokine receptor CXCR4. This allows the neutrophils to migrate toward the tumor cells in a CXCL12-dependent manner, promoting tumor cell survival; (B) Osteopathic melanoma LCP-derived EVs alter the osteotropism of other melanoma cells. EV exposure of SK-Mel28 and WM-266 cells induces plasma membrane ACKR3 expression, resulting in a CXCL12-dependent tumor cell migration toward the bone; (C) EVs derived from prostate cancer cells are rich in PKM2, a kinase that induces CXCL12 production and secretion in bone marrow stem cells. Increased CXCL12 section induces migration of cancer cells toward the bone marrow in a chemokine receptor CXCR4-dependent manner; (D) Breast cancer cells can increase the migration and invasion of other breast cancer cells via EV-mediated transfer of MMP1. MMP1 is a protease that can activate PAR1 receptors on the receiving breast cancer cells in an autocrine manner, resulting in increased migration. PKM2: pyruvate kinase muscle isozyme 2; MMP1: matrix metalloprotease 1; BMSCs: bone marrow stem cells.