Insulinlike growth factor-binding protein modulates the growth response to insulinlike growth factor 1 by human gastric cancer cells

Gastroenterology. 1993 Jun;104(6):1595-604. doi: 10.1016/0016-5085(93)90634-o.


Background: This study determined whether the resistance to the mitogenic effect of insulinlike growth factor 1 (IGF-1) in AGS (we found that IGF-1 had almost no effect on the growth of AGS) cells is caused by the absence of IGF-1 receptor on the cells or by the interference of endogenous IGFs and IGF-binding protein (IGFBP).

Methods: IGF-1 receptors were examined by radioligand binding assay. The protein in conditioned medium and the molecular weight of IGF-1 receptors on AGS cells were determined by affinity cross-linking with 125I-IGF-1 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Messenger RNAs for IGF-1, IGF-2, and IGFBP-4 were detected by Northern analysis.

Results: AGS cells possessed a single class of high-affinity binding sites for IGF-1 (dissociation constant [Kd], 0.51), with a binding capacity approximately 4 x 10(4) sites per cell. The size of the alpha subunit of IGF-1 receptors on cell membranes was approximately 130 kilodaltons. des (1-3) IGF-1, a truncated IGF-1 with very low affinity to IGFBPs, stimulated AGS cell growth in dose-dependent fashion. The medium conditioned by AGS cells contained IGFBPs of 27-32 and 37-42 kilodaltons. AGS cells expressed messenger (mRNA) RNAs for IGF-2 and IGFBP-4 but not for IGF-1, whereas another gastric carcinoma cell line (SIIA), whose growth is stimulated by IGF-1, expressed mRNA IGF-2 but did not express mRNA for IGF-1 or IGFBP-4:

Conclusions: The relative absence of growth response of AGS cells to IGF-1 is due to the endogenously produced IGFBPs sequestering IGF-1 and preventing receptor interaction.

Publication types

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

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Division
  • Culture Media, Conditioned
  • Humans
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor II / genetics
  • Peptide Fragments / pharmacology
  • RNA, Messenger / analysis
  • Receptor, IGF Type 1 / analysis
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured


  • Carrier Proteins
  • Culture Media, Conditioned
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Proteins
  • Peptide Fragments
  • RNA, Messenger
  • insulin-like growth factor 1, des-(1-3)-
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1