Insulin-like growth factor-I and human lung fibroblast-derived insulin-like growth factor-I stimulate the proliferation of human lung carcinoma cells in vitro.
The concentration of insulin-like growth factor I (IGF-I) in tissue taken from human non-small cell lung carcinomas (non-SCLC) is 1.4- to 7-fold higher than in the surrounding normal lung tissue, and thus, IGF-I may be involved in the growth of non-SCLC. We report here that non-SCLC cell lines (A549, A427, SK-LU-1) expressed the IGF-I receptor protein, and IGF-I stimulated the proliferation of low-density plated (2000 cells/cm2 growth area) carcinoma cells by 1.6- to 3-fold above control after a 4-day incubation period under serum-free conditions (A549, A427) or in the presence of 0.25% serum (SK-LU-1). Immunoblot data indicated that IGF-I was not secreted by the lung carcinoma cells; however, IGF-I-like proteins were present in the serum-free medium conditioned by human adult lung fibroblasts (CCD-19Lu). The secretion of the immunoreactive IGF-I-like protein was dependent on the passage level of the fibroblasts. At least one of the IGF-I-like factors promoted the serum-free growth of A549 cells (2-fold increase in cell number over control after 4 days) and stimulated a 3-fold increase in the tyrosine kinase activity of detergent-solubilized IGF-I receptors from A549 cells. Both stimulatory effects were neutralized by an anti-IGF-I antibody, suggesting that the fibroblast-derived factor mediated its activity via the IGF-I receptor. Our data indicate that lung fibroblast-derived IGF-I may stimulate the growth of non-SCLC in vivo.
Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg 24061.
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Ankrapp
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Bevan
D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology*; D008970:Molecular Weight; D017526:Receptor, IGF Type 1 / Q000032:analysis; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1