The role of alpha(v)beta(3) in prostate cancer progression.
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.
Cooper
Carlton R
CR
Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. cacooper@umich.edu
Chay
Christopher H
CH
Pienta
Kenneth J
KJ
D002448:Cell Adhesion; D002465:Cell Movement; D018450:Disease Progression; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism* / Q000502:physiology*; D012795:Sialoglycoproteins / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019096:Vitronectin; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human