The role of alpha(v)beta(3) in prostate cancer progression

Abstract

Integrin alpha(v)beta(3) is involved in varied cell biological activities, including angiogenesis, cell adhesion, and migration on several extracellular matrix components. Although alpha(v)beta(3) 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 alpha(v)beta(3). 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 alpha(v)beta(3) plays in prostate cancer progression, with specific emphasis on bone metastasis and on alpha(v)beta(3) signaling in prostate cancer cells. The data suggest that alpha(v)beta(3), 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.

Figure 1

α_vβ₃ signaling pathway in prostate cancer cells. Ligation of α_vβ₃ with multiple ligands (i.e., osteopontin, BSP, or vitronectin) activates FAK, which interacts and activates PI-3 kinase [23]. The products of PI-3 kinase activity recruit PKB/Akt to the cell membrane where it is activated by phosphorylation and it phosphorylates several substrates to elicit a variety of biological responses, including cell survival, adhesion, and migration. Although NF-κB is potentially involved in the α_vβ₃ signal transduction pathway [8], its role in this signaling pathway is not known for prostate cancer cells.