TGFB1 and neoplasm: Interestingly, the vicious cycle model was proposed to explain how the cancer cells are able to grow and form lesions in the bone, and that: a) growth factors within the bone such as bone morphogenic proteins (BMPs) and TGF-β that are released due to osteoclast activity; and b) factors secreted by tumor cells that have colonized the bone, such as parathyroid hormone related protein (PTHrP), that in turn stimulates bone resorption by upregulating receptor activator of nuclear factor kappa-β (RANKL)—viciously feed each other to support tumor growth in the bone microenvironment [113,114].