In this model, we propose for first time that CD109 released from hBM-MSCs could, at least partially, account for the anti-cancer effect of hBM-MSC-CM, and that CD109 action is linked to inhibition of TGF-β-induced pro-metastatic responses, leading to suppression of EMT, attenuation of migration and invasion, and decrease in stemness, in cancer cells. This evidence concerns the gene CD109 and cancer.