The Suitability of Glioblastoma Cell Lines as Models for Primary Glioblastoma Cell Metabolism.

Abstract

Simple SummaryGlioblastoma (GBM) is a deadly brain tumour with no effective treatments. Recently, new treatments which target the cancer’s unique metabolic properties are beginning to emerge. However, this preclinical research is commonly undertaken in human cell lines which poorly recapitulate the properties of the cancer in situ. This study has examined the metabolic properties of five commonly used GBM cell lines in comparison to healthy brain and GBM tissue. While no cell line faithfully recapitulates GBM, certain lines are useful for aspects of metabolic analysis in GBM cells. We identified three cell lines which accurately reflect the mitochondrial metabolism of GBM tumours, and one cell line suited for studies into glycolysis. In addition to providing detailed metabolic profiles of these commonly used cell lines, this research can guide preclinical experiments to assess the efficacy of desperately needed, novel therapeutics for GBM.In contrast to most non-malignant tissue, cells comprising the brain tumour glioblastoma (GBM) preferentially utilise glycolysis for metabolism via “the Warburg effect”. Research into therapeutics targeting the disease’s highly glycolytic state offer a promising avenue to improve patient survival. These studies often employ GBM cell lines for in vitro studies which translate poorly to the in vivo patient context. The metabolic traits of five of the most used GBM cell lines were assessed and compared to primary GBM and matched, healthy brain tissue. In patient-derived GBM cell lines, the basal mitochondrial rate (p = 0.043) and ATP-linked respiration (p < 0.001) were lower than primary adjacent normal cells from the same patient, while reserve capacity (p = 0.037) and Krebs cycle capacity (p = 0.002) were higher. Three cell lines, U251MG, U373MG and D54, replicate the mitochondrial metabolism of primary GBM cells. Surprisingly, glycolytic capacity is not different between healthy and GBM tissue. The T98G cell line recapitulated glycolysis-related metabolic parameters of the primary GBM cells and is recommended for research relating to glycolysis. These findings can guide preclinical research into the development of novel therapeutics targeting metabolic pathways in GBM.