Expression and synthesis of insulin-like growth factor (IGF)-I, -II and their receptors in human glioma cell lines.

Insulin-like growth factor (IGF)-I and -II are involved in the regulation of brain development and are thought to play a pivotal role in the proliferation of gliomas. Expression of IGF-I, IGF-II, the type I and type II IGF receptor were studied in a panel of thirty glioma cell lines by Northern blotting and PCR analysis. IGF-II mRNA expression with transcripts of 4.8 and 6.0 kb was shown only in one glioma cell line (NCE-G96) and no transcripts for IGF-I, IGF-I-R and IGF-II-R could be detected by Northern analysis in total RNA. However, PCR analysis revealed signals in 19/28 cell lines for IGF-I, 27/30 for ICE-II, 19/28 for IGF-I-R and 22/28 glioma cell lines for IGF-II-R. Additional IGF-I, IGF-II, IGF-I-R and IGF-II-R PCR products were detected which might represent alternative splicing products or variants. In addition, the secretion of IGF-I and IGF-II peptides was measured by radioimmunoassay. IGF receptor status and binding characteristics were established by Scatchard analysis. Proliferation assays showed different effects of IGFs and IGF analogues on the proliferation of these cell lines. Des-(1-3)IGF-I showed an unexpected inhibitory activity on glioma cell proliferation. This may have either been due to a direct effect of the ligand for the induction of a more differentiated state refractory to its action.