In osteoblastic lesions (i.e., osteosarcoma and prostate cancer metastases), tumor-derived growth factors (i.e., insulin growth factors (IGF)-1 and -2, transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), platelet-derived growth factor (PDGF), endothelin-1 (ET-1), and fibroblasts growth factors (FGFs)) stimulate the differentiation and bone-forming activity of osteoblasts. This evidence concerns the gene EDN1 and osteosarcoma.