Investigating the Role of IGF-1 Receptor in Glioma Cell Survival, Migration and Proliferation

Abstract

Glioblastoma (GB) is the most common primary brain tumor, distinctive by its aggressive, highly invasive, angiogenic and necrotic presentation. The Insulin-like growth factor (IGF) pathway plays an important role in cancer cell proliferation, survival and migration. This study was initiated to investigate the role of the IGF-1 receptor in glioma cell survival, migration and proliferation. We tested glioma cells’ response to IGF1 receptor inhibition and whether the response is dependent on the endogenous levels of pIGF1R β (phosphorylated IGF receptor). We used a small molecule inhibitor of IGF1R, Tyrphostin AG1024, to test for dose-dependent apoptosis and for sensitization to the combination treatment with temozolomide, an oral alkylating agent used for the treatment of Grade IV astrocytoma. We also observed that glioma cell migration and proliferation may depend on the endogenous level of pIGF1R β. Because IGF1R is widely expressed in healthy and malignant cells, development of therapeutic uses for IGF1R-inhibitors will require defining additional genomic or proteomic characteristics. This would confer differential vulnerability between tumor and normal cells. Further investigation is needed to determine the molecular predictors of a glioma cell’s response to IGF1R inhibition.