Though the engagement of tetraspanins in GPCR activation is not fully elucidated, GPCR engagement in membrane lipid microdomains / rafts and Exo contributes to the dynamic of intercellular communication including cytoskeleton arrangement and signaling [119–121], where coimmunoprecipitation points towards Tspan8 and CD151 contributing to CD184-promoted homing and settlement of MCA tumor cells within the BM environment. This evidence concerns the gene CXCR4 and neoplasm.