Expression and activation of αvβ3 integrins by SDF‐1/CXC12 increases the aggressiveness of prostate cancer cells

Abstract

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 α_vβ₃ 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 α_vβ₃ receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF‐1 transiently increased the expression of β₃ 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 α_vβ₃ receptors. Activation and increased expression of α_vβ₃ within SDF‐1‐rich organs may participate in metastatic localization. Prostate 67:61–73, 2007.