Integrin αvβ3 Signaling in Tumor-Induced Bone Disease

Tumor-induced bone disease is common among patients with advanced solid cancers, especially those with breast, prostate, and lung malignancies. The tendency of these cancers to metastasize to bone and induce bone destruction is, in part, due to alterations in integrin expression and signaling. Substantial evidence from preclinical studies shows that increased expression of integrin alpha v beta 3 in tumor cells promotes the metastatic and bone-invasive phenotype. Integrin alpha v beta 3 mediates cell adhesion to several extracellular matrix proteins in the bone microenvironment which is necessary for tumor cell colonization as well as the transmission of mechanical signals for tumor progression. This review will discuss the alpha v beta 3 integrin receptor in the context of tumor-induced bone disease. Specifically, the focus will be the role of alpha v beta 3 in modulating cancer metastasis to bone and tumor cell response to the bone microenvironment, including downstream signaling pathways that contribute to tumor-induced osteolysis. A better understanding of integrin dysregulation in cancer is critical to developing new therapeutics for the prevention and treatment of bone metastases.