TGFB1 and neoplasm: These factors directly stimulate osteoclast-mediated bone resorption and lead to the release of bone-derived tumor growth factors such as TGF-β, insulin-like growth factors (IGF), platelet-derived growth factor (PDGF), and bone morphogenetic protein (BMP) in the bone matrix, which promotes tumor growth in bone metastases (157, 158).