Expression and Activation of Alpha v Beta 3 Integrins by SDF-1/CXC12 Increases the Aggressiveness of Prostate Cancer Cells

Prostate. 2007 Jan 1;67(1):61-73. doi: 10.1002/pros.20500.

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 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism
  • Chemokines, CXC / physiology*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Integrin alphaVbeta3 / biosynthesis*
  • Integrin alphaVbeta3 / genetics*
  • Integrin alphaVbeta3 / metabolism
  • Integrin alphaVbeta3 / physiology
  • Male
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Phenotype
  • Phosphorylation
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Tumor Cells, Cultured

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Integrin alphaVbeta3