TNFSF11 and neoplasm: While the initial shift is often induced by factors secreted by tumor cells such as RANKL and PTHrP, the resulting degradation of bone releases a substantial supply of insulin like growth factors I and II (IGF-I, IGF-II), TGF-β, platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) along with bone morphogenetic proteins (BMP) and other factors from the ECM which in turn promote tumor growth and development.