CHARACTERIZATION OF INSULIN-LIKE GROWTH FACTOR-I RECEPTORS AND GROWTH EFFECTS IN HUMAN LUNG-CANCER CELL-LINES

Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines were studied for insulin-like growth factor I (IGF-I) receptor expression and with regard to the influence of IGF-I on cell proliferation. IGF-I receptors on the cells were characterized by competitive binding assays, chemical crosslinking and northern blot hybridization of IGF-I receptor mRNA. All SCLC and NSCLC cell lines showed specific IGF-I binding sites with an affinity (K(D)) of 0.69-5.21 nM. The amount of binding sites ranged from 59 fmol/mg to 1230 fmol/mg protein. The IGF-I binding was inhibited by the IGF-I receptor antibody (alpha-IR-3). Northern blot hybridization indicated that IGF-I receptor mRNA was being produced by all SCLC and NSCLC cell lines. We used the soft-agarose clonogenic assay to evaluate the influence of IGF-I on the in vitro proliferation of the cells. Our results have shown that IGF-I stimulates the growth of all tested cell lines ranging from a factor of 1.6 to 4.2 in SCLC and from 1.1 to 2.7 in NSCLC. The data indicate that the IGF-I receptor thus appears to be the common pathway for the mitogenic activity of IGF-I and IGF-II with regard to human lung cancer cells.