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

• Published in: Cancer research (Chicago, Ill.) Ill.), 1993-07, Vol.53 (14), p.3399-3404
• Main Authors: ANKRAPP, D. P, BEVAN, D. R
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - chemistry; Carcinoma, Non-Small-Cell Lung - pathology; Cell Division - drug effects; Culture Media, Conditioned - chemistry; Dose-Response Relationship, Drug; Fibroblasts - metabolism; Humans; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Lung Neoplasms - chemistry; Lung Neoplasms - pathology; Medical sciences; Molecular Weight; Pneumology; Receptor, IGF Type 1 - analysis; Tumor Cells, Cultured; Tumors of the respiratory system and mediastinum
• ISSN: 0008-5472; 1538-7445

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.