Insulin and Insulin-Like Growth Factor I in Brain Tumors: Binding and in Vitro Effects

We have measured insulin and insulin-like growth factor I (IGF-I) binding in human gliomas, meningiomas, and normal brain and studied the effect of insulin on the morphology, proliferation, and differentiation of central nervous system tumor and normal fetal cells in culture. Specific 125I-insulin and 125I-IGF-I binding was demonstrated by competition-inhibition binding assays. Insulin binding was measured in plasma membrane preparations from 9 freshly isolated human meningiomas, 4 glioblastomas multiforme (GBMs), a low-grade glioma, a normal adult brain, and a fetal brain. IGF-I binding was measured in similar preparations from 5 meningiomas, 4 GBMs, a low-grade glioma, and a normal adult brain. Incubations were carried out at 4°C for 18 to 20 hours. Meningiomas showed higher specific insulin binding per 0.25 mg of protein than GBMs (19% versus 3%, P < 0.005), and this difference was not related to small differences observed in insulin degradation. By contrast, IGF-I binding was significantly higher in gliomas than in meningiomas (27% versus 12%, P < 0.005). Also, IGF-I binding was significantly higher than insulin binding in GBMs (27% versus 3%, P < 0.03); binding of both IGF and insulin was high in meningiomas. In normal adult brain IGF-I and insulin binding was 7 to 10%. The ability of insulin to support and enhance the growth of central nervous system tumor cells in culture was investigated. Cell cultures were derived from a freshly isolated glioblastoma, a low-grade glioma, and 3 meningiomas. Cells initially grown in serum were exposed to either serum-containing media, serum-free media (SFM), or SFM supplemented with 30 μg of insulin/ml. In contrast to SFM, insulin added to SFM maintained cell survival and significantly increased proliferation, similar to serum in low-grade glioma and meningioma cells (P < 0.05) and induced morphological changes suggestive of differentiation in the tumors studied. Moreover, insulin sustained the ability of GBM cells to stain for glial filament acidic protein, which was lost in SFM. Similar studies were performed with normal fetal brain cells and comparable effects of insulin were observed. (Neurosurgery 24:791-797, 1989)