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Tumor Biology |
vß3Integrin Is Modulated by a Focal Adhesion Kinase Pathway1
Departments of Pathology [D-Q. Z., M. F., G. T., L. R. L.] and Biology [A. S. W.], Yale University School of Medicine, New Haven, Connecticut 06520
The highly invasive human prostate cancer PC3 cell line was found to express the 
vß3 integrin; in contrast, the noninvasive LNCaP prostate cancer cell line did not express vß3. PC3 cells adhered to and migrated on vitronectin (VN), an vß3 ligand expressed in mature bone where prostate cancer cells preferentially metastasize. In contrast, LNCaP cells did not adhere to or migrate on VN. Analysis of primary human prostate cancer cells isolated from 16 surgical specimens, showed that these cells expressed vß3, whereas normal prostate epithelial cells did not. In addition, only primary prostate cancer cells adhered to and migrated on VN. The role of vß3 in mediating prostate epithelial cell migration was confirmed using LNCaP cell transfectants expressing ß3 (ß3-LNCaP). Exogenous expression of vß3 induced LNCaP cells to adhere to and migrate on VN. In response to vß3 engagement, increased tyrosine phosphorylation of focal adhesion kinase (FAK), a signaling molecule activated by integrins and able to modulate cell migration, was detected. Transfection of FAK-related nonkinase, known to compete with FAK for its correct localization and phosphorylation, caused inhibition of ß3-LNCaP cell migration, specifically on VN. These data indicate that de novo expression of vß3 integrin in prostate cancer cells generates a migratory phenotype that is modulated by a FAK signaling pathway. This study points to vß3 as potential target in prostate cancer cell invasion and metastasis.
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