Expression and activation of alpha(V)beta(3) integrins by SDF-I/CXCI2 increases the aggressiveness of prostate cancer cells

BACKGROUND. Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key elements in the metastasis of prostate cancer cells to bone-but the mechanisms as to how it localizes to the marrow remains unclear. METHODS. Prostate cancer cell lines were stimulated with SDF-1 and evaluated for alterations in the expression of adhesion molecules using microarrays, FACs, and Western blotting to identify alpha(v)beta(3) receptors. Cell-cell adhesion and invasion assays were used to verify that activation of the receptor is responsive to SDF-1. RESULTS. We demonstrate that SDF-1 transiently regulates the number and affinity of alpha(v)beta(3) receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased the expression of beta(3) receptor subunit and increased its phosphorylation in metastatic but not nonmetastatic cells. CONCLUSIONS. The transition from a locally invasive phenotype to a metastatic phenotype may be primed by the elevated expression Of alpha(v)beta(3) receptors. Activation and increased expression of alpha(v)beta(3) within SDF-1-rich organs may participate in metastatic localization.