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

Yan Xi Sun, Ming Fang, Jianhua Wang, Carlton R. Cooper, Kenneth J. Pienta, Russell S. Taichman

Research output: Contribution to journalArticlepeer-review

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 αvβ3 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 αvβ 3 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 αvβ3 receptors. Activation and increased expression of αvβ 3 within SDF-1-rich organs may participate in metastatic localization.

Original languageEnglish (US)
Pages (from-to)61-73
Number of pages13
JournalProstate
Volume67
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Keywords

  • Bone
  • Integrin αβ
  • Metastasis
  • Prostate cancer
  • SDF-1
  • β phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Urology

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