Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop

Int J Cancer. 1994 Aug 1;58(3):452-9. doi: 10.1002/ijc.2910580325.


Insulin-like growth factors (IGFs) are potent proliferation stimulators for numerous tumor cells and often function as autocrine growth factors. We have previously shown that exogenous IGF-I and IGF-II enhance proliferation of colorectal carcinoma cells. The biological signal of both factors is transmitted through the IGF-I receptor (IGF-I-R). This receptor was expressed in 12/12 colorectal carcinoma cell lines tested. alpha IR3, a neutralizing monoclonal antibody (MAb) directed against the human IGF-I-R, inhibited proliferation in 7/12 lines (Caco-2, HT-29, LS411N, LS513, LS1034, WiDr and SW620), as reflected by a reduction of MTT conversion (19 to 42%), a decrease in cell number (39 to 72%) and an increase in doubling time (up to 2-fold). In addition, in 4 cell lines (Caco-2, LS513, LS1034, WiDr) alpha IR3 suppressed colony formation in methylcellulose (40 to 84%). Excess of exogenous IGF completely neutralized alpha IR3-mediated inhibitory effects. Northern blot analysis revealed abundant expression of 2 IGF-II transcripts of 5.0 and 4.3 kb in LS1034 cells. In addition, we observed that growth inhibition by alpha IR3 was correlated with a more differentiated phenotype. Our results suggest that growth of many colorectal carcinoma cell lines is regulated by autocrine IGF-II-mediated stimulation of the IGF-I-R.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Blotting, Northern
  • Cell Adhesion
  • Cell Division / drug effects
  • Cell Division / physiology
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / ultrastructure*
  • Culture Media
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor II / biosynthesis
  • Insulin-Like Growth Factor II / physiology*
  • Methylcellulose
  • Neoplastic Stem Cells / drug effects
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / immunology
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Culture Media
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Methylcellulose
  • Receptor, IGF Type 1