Expression and Activation of [alpha]v[beta]3 Integrins by SDF-1/CXC12 Increases the Aggressiveness of Prostate Cancer Cells.
Sun, Yan-Xi 1; Fang, Ming 2; Wang, Jianhua 1; Cooper, Carlton R. 3; Pienta, Kenneth J. 4; Taichman, Russell S. 1,*
[Article]
Prostate.
67(1):61-73, January 1, 2007.
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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.
Copyright (C) 2007 John Wiley & Sons, Inc.
