Insulin-like growth factor binding protein-3 inhibits migration of endometrial cancer cells

Cancer Lett. 2012 Apr 1;317(1):41-8. doi: 10.1016/j.canlet.2011.11.011. Epub 2011 Nov 13.

Abstract

Cell migration and invasion leading to metastasis is a major cause of death from endometrial cancer (EC). We have shown that the rate of EC cell migration is inversely related to the level of insulin-like growth factor protein-3 (IGFBP-3). Down-regulation of IGFBP-3 by siRNA in EC cells accelerated migration without affecting proliferation and cells displayed a more migratory phenotype, with co-localization of migration-associated markers at the leading edge of cell membranes. Opposite effects were seen with either the addition of recombinant IGFBP-3 or overexpression of IGFBP-3. Cells with mutated PTEN had the highest IGFBP-3 expression and the slowest migration rates. This study demonstrates that endogenous IGFBP-3 modulates adhesion-migration dynamics in EC cells, implying that it may be important in regulating metastasis in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Focal Adhesions / metabolism
  • Genotype
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Mutation
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phenotype
  • RNA Interference
  • Recombinant Proteins / metabolism
  • Time Factors
  • Transfection

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Recombinant Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human