We show for the first time that (A) V2R activity in ccRCC tumor cells is important for fibroblast activation, migration, and proliferation, (B) V2R regulates the production of secreted factors from ccRCC tumor cells that are known to activate CAFs, and (C) secretion of the factors, including CCL2, CCL5, GM-CSF, IL8, TSP1, and TFPI-1 are regulated by a V2R and YAP -dependent mechanism in ccRCC cells. Here, CSF2 is linked to nonpapillary renal cell carcinoma.