The role of α_vβ₃ in prostate cancer progression

Integrin α_vβ₃ is involved in varied cell biological activities, including angiogenesis, cell adhesion, and migration on several extracellular matrix components. Although α_vβ₃ is not typically expressed in epithelial cells, it is expressed in macrophages, activated leukocytes, cytokine- stimulated endothelial cells, osteoclasts, and certain invasive tumors. Interestingly, the adhesion and migration of breast cancer cells on bone matrix are mediated, in part, by α_vβ₃. Similar to breast cancer cells, prostate cancer cells preferentially metastasize to the bone. The biological events that mediate this metastatic pattern of prostate cancer are not well defined. This review discusses the role α_vβ₃ plays in prostate cancer progression, with specific emphasis on bone metastasis and on α_vβ₃ signaling in prostate cancer cells. The data suggest that α_vβ₃, in part, facilitates prostate cancer metastasis to bone by mediating prostate cancer cell adhesion to and migration on osteopontin and vitronectin, which are common proteins in the bone microenvironment. These biological events require the activation of focal adhesion kinase and the subsequent activation of PI-3 kinase/Akt signaling pathway.