Abstract 5427: Distinctions between the metabolic changes in glioblastoma cells and glioma stem-like cells following irradiation

Abstract

Abstract Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults and, even with aggressive treatment that includes surgical resection, radiation, and temozolomide administration, prognosis is poor due to tumor recurrence. There is evidence that within GBMs a small number of glioma stem- like cells (GSCs) exist, which are thought to be radiation resistant and may be capable of repopulating a tumor after treatment. Like most cancers, GBMs largely employ aerobic glycolysis to create ATP, a phenomenon known as the Warburg effect. Experiments have shown that the cellular metabolism of GSCs differs from that of differentiated cells, making them an attractive target for novel therapeutic approaches. Much work has been done to analyze the metabolic profiles of GSCs with the goal of identifying potential therapeutic targets, but little data exists linking metabolic changes to radiation resistance. The purpose of this study is to characterize the metabolic differences between glioma stem- like cells and traditional GBM tumor cells with and without radiation treatment (IR). To this end, we compared the metabolism of a human derived GSC line with two commonly used GBM cell lines before and after IR. At baseline, we find that glioma stem-like cells are more quiescent than GBM cells, which have higher levels of both glycolysis and oxidative phosphorylation. GBM lines show higher levels of both basal and maximal respiration, as well as basal glycolysis and glycolytic capacity than GSCs. They also express higher levels of energy, glycolysis, and TCA cycle metabolites than GSCs. Inversely, GSCs demonstrate metabolic signs of quiescence such as decreased NEAA synthesis. After IR, the radiation- sensitive GBM tumor cell line (U251) exhibits increases in all metabolic pathways, whereas the levels of glycolytic and oxidative metabolites in the GSCs remain unchanged. All cell lines show an increase of ATP and NAD production following IR. These findings indicate that the metabolism of GSCs undergoes different alterations than that of GBM tumor cells after IR, making them an attractive target for novel therapeutic approaches in conjunction with radiation therapy. Additionally, differences in metabolic signatures between GSC lines could be useful for non-invasive diagnostic modalities such as 13C MR spectroscopy. Citation Format: Elizabeth I. Spehalski, Cord Peters, Philip Tofilon, Kevin Camphausen. Distinctions between the metabolic changes in glioblastoma cells and glioma stem-like cells following irradiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5427. doi:10.1158/1538-7445.AM2017-5427