Expression and function of the insulin‐like growth factor I system in human non‐small‐cell lung cancer and normal lung cell lines

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Abstract
In order to analyze the presence and the function of the “insulin‐like growth factor 1 (IGF‐1) system” in human non‐small‐cell lung cancer (N‐SCLC) we tested 5 cell lines of different histological sub‐types: A549, Ca‐Lu‐6, SK‐Lu‐1 (adenocarcinoma); Ca‐Lu‐1, SK‐Mes‐1 (squamous carcinoma) and one normal fibroblast‐like fetal lung cell line (IMR‐90) for expression of the IGF‐1 peptide and its RNA transcribed from the IGF‐1 gene; IGF‐binding proteins (IGF‐BP); IGF‐1 receptor (IGF‐1‐R) and its mRNA. In addition, we examined the capacity of exogenous human recombinant IGF‐1 to enhance the in vitro cell proliferation. In medium conditioned from cell cultures, we detected immunoreactive IGF‐1 material by radioimmunoassay. Western ligand blot and affinity labelling demonstrated the presence of several molecular species of IGF‐BPs (IGF‐BP‐4, −1, −2, −3) as well. Northern blot analysis of polyA+ RNA from all cell lines examined revealed the presence of IGF‐1 and IGF‐1‐R mRNA. Moreover, binding studies on cultured cell lines showed one class of high‐affinity, operative type‐1 IGF cell‐surface binding sites. Finally, by thymidine uptake and colorimetric metabolic MTT assays, we found that most neoplastic cell lines react mitogenically to IGF‐1 and that its physiological effect is abolished by an anti‐IGF‐1‐receptor antibody. These data indicate the importance of the IGF‐1 system in N‐SCLC growth. Furthermore, they suggest that this mitogenic complex should be appraised as a possible target for anti‐neoplastic drugs, antibodies or growth‐factor analogues offering potential new approaches to therapy.
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