Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility

Endocr Relat Cancer. 2009 Sep;16(3):795-808. doi: 10.1677/ERC-08-0175. Epub 2009 Jun 9.


IGF-binding protein-3 (IGFBP-3) is a modulator of the IGF-signaling pathway and was described as an anti-cancer agent in prostate cancer. The molecular mechanisms underlying these effects remained, however, largely undefined. We analyzed the influence of recombinant IGFBP-3 on cell proliferation of PC3, Du145, and LNCaP prostate cancer cells. As expected, IGFBP-3 inhibited IGF-stimulated cell proliferation by blocking IGF-mediated proliferation signals, but we observed an IGF-independent inhibitory effect of IGFBP-3 on prostate cancer cell proliferation in long-term cultures. We further investigated the influence of IGFBP-3 on adhesion, motility, and invasion of prostate cancer cells using adhesion assays, live-cell imaging techniques, and matrigel invasion measurements. There was a clear inhibitory effect of IGFBP-3 on tumor cell adhesion to extracellular matrix components in the presence and absence of IGF, whereas cell-cell adhesion was not affected. The same inhibitory effect of IGFBP-3 was determined on cell motility when real-time cell movements were followed. In addition, IGFBP-3 was able to inhibit tumor cell invasion through matrigel. In summary, we show that IGFBP-3 inhibits proliferation, adhesion, migration, and invasion processes of prostate tumor cells. These newly described mechanisms of IGFBP-3 can be of importance for tumor progression and support a role of IGFBP-3 in therapeutic settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Line, Transformed
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / pharmacology*
  • Insulin-Like Growth Factor Binding Protein 3 / physiology
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Cells, Cultured


  • Insulin-Like Growth Factor Binding Protein 3