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

Guo YS, Beauchamp RD, Jin GF, Townsend CM, Thompson JC
Gastroenterology. 1993 104 (6): 1595-604

PMID: 7684715 · 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.

MeSH Terms (14)

Adenocarcinoma Carrier Proteins Cell Division Culture Media, Conditioned Humans Insulin-Like Growth Factor Binding Protein 4 Insulin-Like Growth Factor Binding Proteins Insulin-Like Growth Factor I Insulin-Like Growth Factor II Peptide Fragments Receptor, IGF Type 1 RNA, Messenger Stomach Neoplasms Tumor Cells, Cultured

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