Department of medicine, Division of Endocrinology, Indiana University, Indianapolis, Indiana, USA.
Curr Pharm Des. 2010;16(11):1301-12. doi: 10.2174/138161210791034049.
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.
乳腺癌和前列腺癌常转移至骨骼并导致骨质破坏。在骨骼组织中，转化生长因子-β（TGF-β）是一种主要的骨源性因子，负责驱动乳腺癌在骨骼中的正向恶性循环。TGF-β 被破骨细胞吸收以活性形式从骨中释放，并增加肿瘤分泌的因子，刺激肿瘤附近骨的溶骨性破坏。此外，它还激活上皮-间充质转化和肿瘤细胞浸润，增加血管生成并诱导免疫抑制。阻断 TGF-β 信号通路以打断肿瘤与骨骼之间的这种恶性循环，为减少骨骼转移提供了治疗干预的靶点。在这里，我们总结了 TGF-β 在骨转移中的现有知识，TGF-β 抑制剂的应用及其在临床应用中的潜力和后果。
