Mapping of Metabolic Heterogeneity of Glioma Using MR-Spectroscopy.
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ABSTRACT:
SUBMITTER: Franco P
PROVIDER: S-EPMC8155922 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Mapping of Metabolic Heterogeneity of Glioma Using MR-Spectroscopy.
Franco Pamela P Huebschle Irene I Simon-Gabriel Carl Philipp CP Dacca Karam K Schnell Oliver O Beck Juergen J Mast Hansjoerg H Urbach Horst H Wuertemberger Urs U Prinz Marco M Hosp Jonas A JA Delev Daniel D Mader Irina I Heiland Dieter Henrik DH Heiland Dieter Henrik DH
Cancers 20210517 10
Proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) delivers information about the non-invasive metabolic landscape of brain pathologies. <sup>1</sup>H-MRS is used in clinical setting in addition to MRI for diagnostic, prognostic and treatment response assessments, but the use of this radiological tool is not entirely widespread. The importance of developing automated analysis tools for <sup>1</sup>H-MRS lies in the possibility of a straightforward application and simplified interpretatio ...[more]
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Project description:BackgroundGlioblastomas have been shown to rely on glycolysis as an energy source. However, recent evidence suggests that at least a subset of glioma cells with stem cell-like properties can thrive on oxidative phosphorylation. It remains unclear whether both metabolic phenotypes support tumor propagation, if they are independent, and how stable they are. The present study investigated these questions with the use of isogenic murine glioma stem cells (GSCs).MethodsGSCs were established from tumors formed by Ink4a/Arf-null, H-RasV12-expressing glioma-initiating cells that differed in extracellular acidification potential. Metabolic characteristics of GSCs were determined by measurement of glucose, oxygen, and glutamine uptake, ATP content, and lactate production. Effects of metabolic inhibitors and changes in oxygen or nutrient availability on lactate production and tumorsphere growth were also determined.ResultsGSCs were found either to consume more glucose and produce more lactate or to consume more oxygen and maintain a higher ATP content depending on the metabolic characteristics of the tumor cells of origin. The latter, mitochondrial-type GSCs increased lactate production after treatment with the oxidative phosphorylation inhibitor oligomycin or phenformin. Exposure to hypoxia also increased lactate production and expression of glycolysis-related enzymes and metabolites in mitochondrial-type GSCs in a reversible manner.ConclusionsBoth glycolytic and mitochondrial-type energy production can sustain tumor propagation by isogenic GSCs. Whereas both phenotypes can be independent and stable, cells that rely on oxidative phosphorylation can also switch to a more glycolytic phenotype in response to metabolic stress, suggesting that plasticity is a further characteristic of GSC metabolism.
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