EXPRESSION AND SYNTHESIS OF INSULIN-LIKE GROWTH-FACTOR (IGF)-I, (IGF)-II AND THEIR RECEPTORS IN HUMAN GLIOMA CELL-LINES

Insulin-like growth factor (IGF)-I and -II are involved in the regulat ion 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 li nes 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 reve aled signals in 19/28 cell lines for IGF-I, 27/30 for ICE-II, 19/28 fo r 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 re present alternative splicing products or variants. In addition, the se cretion of IGF-I and IGF-II peptides was measured by radioimmunoassay. IGF receptor status and binding characteristics were established by S catchard analysis. Proliferation assays showed different effects of IG Fs and IGF analogues on the proliferation of these cell lines. Des-(1- 3)IGF-I showed an unexpected inhibitory activity on glioma cell prolif eration. This may have either been due to a direct effect of the ligan d for the induction of a more differentiated state refractory to its a ction.