Tgf-Beta pathway as a therapeutic target in bone metastases.
Breast and prostate cancer frequently metastasizes to the skeleton and causes bone destruction. In skeletal tissue, transforming growth factor-beta (TGF-beta) is a major bone-derived factor responsible for driving a feed-forward vicious cycle of breast cancer growth in bone. TGF-beta is released from bone in active form by osteoclastic resorption and increases the tumor secretion of factors, which stimulate osteolytic destruction of the bone adjacent to the tumor. Moreover it activates epithelial-mesenchymal transition and tumor cell invasion, increases angiogenesis and induces immunosuppression. Blocking the TGF-beta signaling pathway to interrupt this vicious cycle between tumor and bone offers a target for therapeutic intervention to decrease skeletal metastasis. Here we summarize the current knowledge of TGF-beta in bone metastases, the use of TGF-beta inhibitors and its potential for clinical use and consequences.
Juárez
Patricia
P
Department of medicine, Division of Endocrinology, Indiana University, Indianapolis, Indiana, USA.
Guise
Theresa A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology* / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D016212:Transforming Growth Factor beta