EXTH-11. GLIOBLASTOMA STEM CELL GROWTH DEPENDENCE ON NUTRIENTS: MORE THAN BASAL METABOLIC ACTIVITIES. (5th November 2018)

• Record Type: Journal Article
• Authors: Zhang, Chen; Ding, Jie; Jeong, Kang Jin; Park, Soon Young; Wu, Shaofang; Li, Xiaolong; Gao, Feng; Yung, W K Alfred; Koul, Dimpy
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi87
• Page End: vi87
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.360
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Deregulated uptake of glucose and amino acids is one of the hallmarks of cancer metabolism. Clinical trials and numerous drugs have been designed to target cancer cell metabolism, however, the effect on cell growth inhibition and how tumor cell metabolism couples with cell growth remain unclear. In this study, we report the glioblastoma stem cells (GSCs) growth dependence on nutrients (glucose, amino acid, and fatty acid) and oxygen. We show that the basal metabolic activities are unable to reflect the extent of proliferation inhibition by metabolic inhibitors. 2-DG (20mM) downregulated extracellular acidification rate (ECAR) more effectively in GSCs with higher glycolytic activity (Pearson r=0.71, p=0.08), the basal glycolytic activity, however, was not significantly correlated with glycolysis inhibitor (2-Deoxy-D-glucose, 2-DG) sensitivity (Pearson r=0.35, p=0.44), indicating basal glycolytic activity cannot predict GSC response to glycolysis inhibitor. Similarly, basal oxidative phosphorylation (OXPHOS) activity also failed to predict GSC responses to OXPHOS inhibition. Although GSCs showed the consistent susceptibility against oligomycin (complex V inhibitor) and hypoxia (Pearson r=0.61, p=0.15), there is no significant correlation between basal oxygen consumption rate (OCR) and oligomycin/hypoxia-induced proliferation inhibition. Thus, both basal glycolytic and basal OXPHOS activities were unable to explain their roles in GSC growth. Studies are underway to investigate the effect of fatty acid and amino acid on tumor growth. As drugs targeting cancer metabolic processes always show dose-limiting toxicity, our study will focus on identifying new "druggable" targets according to GSC nutrient dependences and developing specific therapeutic strategy for GBM populations with certain nutrient dependence.