Blockade of the Type I Somatomedin Receptor Inhibits Growth of Human Breast Cancer Cells in Athymic Mice

J Clin Invest. 1989 Nov;84(5):1418-23. doi: 10.1172/JCI114315.

Abstract

Insulin and insulin-like growth factors (IGIs) stimulate the growth of human breast cancer cells in vitro. The type I somatomedin receptor (SR) expressed in these cells may mediate the growth effects of these peptides. We have examined the role of this receptor on human breast cancer growth with a monoclonal antibody (alpha-IR-3) that blocks the receptor binding domain and inhibits IGF-I-induced growth. alpha-IR-3 inhibited clonal growth in vitro and blocked the mitogenic effect of exogenous IGF-I in both MCF-7 and MDA-231 breast cancer cell lines. Antibody-induced blockade of the type I SR also inhibited the estrogen-independent MDA-231 cells growing in vivo in nude mice, but growth of the estrogen-dependent MCF-7 cells was unaffected. IGIs are important growth regulators of MDA-231 breast cancer cells. Blockade of this growth stimulatory pathway may provide a new treatment strategy.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Cell Division
  • Female
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / pathology*
  • Neoplasms, Experimental / therapy
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / physiology*
  • Receptors, Somatomedin
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Receptors, Cell Surface
  • Receptors, Somatomedin
  • Insulin-Like Growth Factor I