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. Here, PTHLH is linked to neoplasm.