TGFB1 and neoplasm: The aforementioned factors trigger the release of signaling molecules from the bone, including receptor activator of nuclear factor kappa beta ligand (RANKL), osteoprotegerin (OPG), transforming growth factor-beta (TGF-β), insulin-like growth factors (IGFs), platelet-derived growth factor (PDGF), and calcium (Ca), which in turn stimulate tumor proliferation and perpetuate the vicious cycle related to bone metastases.