Effects of Insulin-Like Growth Factors (IGFs) and IGF Receptor Antibodies on the Proliferation of Human Breast Cancer Cells

Growth Factors. 1992;6(4):327-36. doi: 10.3109/08977199209021544.

Abstract

It has been shown previously that MCF-7 cells proliferate in response to nanomolar concentrations of IGF-I and IGF-II. It has also been reported that the actions of both peptides are mediated through the IGF-I receptor. To further characterize these observations, we used MCF-7 and Hs578T cell lines in the serum-free/phenol red-free system developed by Ogasawara and Sibarsku, 1988. Cell proliferation was studied in the presence of insulin, IGF-I and -II and a series of growth factor receptor antibodies. No effect was observed on Hs578T cell proliferation with any of the growth factors. However, MCF-7 cells were stimulated 4-5 fold with IGF-I and insulin, while IGF-II was only slightly less potent. alpha IR3, a monoclonal antibody directed against the IGF-I receptor, was stimulatory when added alone. However, alpha IR3 blocked approximately 50% of the IGF-I response, only 5% of the insulin response, and did not block the IGF-II effect on cell proliferation. These data suggest that alpha IR3 and IGF-I are acting as agonists through the IGF-I receptor, but that insulin and IGF-II are acting through other receptors. Two different IGF-II/M-6-P receptor antibodies and an insulin receptor antibody failed to significantly block IGF-II actions. All three antibodies were stimulatory when added alone. beta-gal inhibited 27% of the IGF-II response and had no effect when added alone. Since beta-gal decreases the binding affinity of the IGF-II/M-6-P receptor for IGF-II and does not bind to the IGF-I or insulin receptor, these data suggest the possibility that IGF-II mitogenic action is mediated through the IGF-II/M-6-P receptor. In summary, these data indicate that nanomolar concentration of insulin, IGF-I and IGF-II are potent mitogens in MCF-7 cells and can potentially stimulate cell proliferation through all three receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Antibodies / pharmacology*
  • Antibodies, Monoclonal / pharmacology*
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cell Line
  • Cell Membrane / metabolism
  • Female
  • Humans
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / isolation & purification
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor II / isolation & purification
  • Insulin-Like Growth Factor II / metabolism
  • Insulin-Like Growth Factor II / pharmacology*
  • Kinetics
  • Receptor, IGF Type 1 / immunology
  • Receptor, IGF Type 1 / isolation & purification
  • Receptor, IGF Type 1 / physiology*
  • Receptor, IGF Type 2 / immunology
  • Receptor, IGF Type 2 / isolation & purification
  • Receptor, IGF Type 2 / physiology*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Insulin
  • Receptor, IGF Type 2
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1