SPP1 and osteosarcoma: Disruption of the TGFβ signaling pathway in osteosarcoma cells either through the overexpression of a natural TGFβ/Smad signaling inhibitor Smad7 or through the use of TGFβ inhibitors such as halofuginone prevented the expression of TGFβ target genes, including RANKL, IL11, CXCR4, VEGF and osteopontin, which slowed down primary tumor growth, reduced bone osteolysis and metastatic burden [32,33].