The role of TGF-β in bone metastasis: novel therapeutic perspectives.

ABSTRACT: The skeleton is a preferred site for cancer metastasis. These bone metastases cause dysregulated bone remodeling and the associated morbidity of fractures, pain, hypercalcemia and catastrophic nerve compression syndromes. Transforming growth factor-β (TGF-β) is stored in mineralized bone matrix, and released and activated by osteoclastic bone resorption. Once activated, TGF-β stimulates nearby metastatic tumor cells within the bone microenvironment to secrete factors that further drive osteolytic destruction of the bone. Therefore, TGF-β and its signaling constitute a critical component driving the feed-forward vicious cycle of cancer growth in bone. Moreover, additional pro-tumorigenic activities attributed to TGF-β include activation of epithelial-to-mesenchymal transition, increased tum

SUBMITTER: Buijs JT 

PROVIDER: S-EPMC3727840 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature