The GPCRs are the largest family of transmembrane proteins involved in multiple biological processes, including bone development and remodeling (7, 8), inflammation/immune response (9), tumor growth, and metastasis (10), etc. A growing body of evidence suggests that GPCRs serve as pro-tumor (GPR56 (11), GPR110 (12), PTHR1 (13), PAR1 (14), S1PR3 (15)) or anti-tumor (GPER1 (16), A3AR (17)) in OS. This evidence concerns the gene S1PR3 and neoplasm.