TGF-β in cancer and bone: implications for treatment of bone metastases.
Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.
Juárez
Patricia
P
Department of Medicine, Division of Endocrinology, Indiana University, Indianapolis, IN, USA.
Guise
Theresa A
TA
D001855:Bone Marrow Diseases / Q000628:therapy; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy*; D016723:Bone Remodeling; D001862:Bone Resorption / Q000628:therapy; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D005544:Forecasting; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology* / Q000627:therapeutic use
D016212:Transforming Growth Factor beta