Biology of insulin-like growth factor binding protein-4 and its role in cancer (review)

Int J Oncol. 2006 Jun;28(6):1317-25.


Insulin-like growth factor binding protein-4 (IGFBP-4) is an important member of the insulin-like growth factor (IGF) system. The IGFBP-4 has three domains of which the N-terminal sequence is important for the binding of IGF. It acts as a transport protein for IGF-I and IGF-II and modulates their biological effects. There is increasing evidence that IGFBP-4 inhibits IGF-induced cellular growth both in vitro and in vivo. IGFBP-4 can also mediate its actions through a mechanism independent of IGFs. IGFBP-4 level and expression in various tissues are influenced by IGFBP protease, nutrition, several growth factors and hormones. Overexpression of IGFBP-4 in transgenic animal models causes reduced growth of organs containing smooth muscle. Most cancers express IGFBP-4 at levels which correlate with their state of differentiation. However, the effects of IGFBP-4 on tumor growth are uncertain. In vitro studies have shown that overexpression of IGFBP-4 inhibit the growth of some colon cancer cells. Overexpression of IGFBP-4 in vivo has been reported to decrease the growth of prostate cancer. The effect of altered expression of IGFBP-4 in vivo in colon and other cancers needs to be explored as locally available IGFs appear to stimulate mitogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Insulin-Like Growth Factor Binding Protein 4 / genetics
  • Insulin-Like Growth Factor Binding Protein 4 / pharmacology
  • Insulin-Like Growth Factor Binding Protein 4 / physiology*
  • Male
  • Neoplasms / pathology*
  • Prostatic Neoplasms / pathology


  • Insulin-Like Growth Factor Binding Protein 4