title: Metabolic state of glioma stem cells and nontumorigenic cells.
abstract: Gliomas contain a small number of treatment-resistant glioma stem cells (GSCs), and it is thought that tumor regrowth originates from GSCs, thus rendering GSCs an attractive target for novel treatment approaches. Cancer cells rely more on glycolysis than on oxidative phosphorylation for glucose metabolism, a phenomenon used in 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography imaging of solid cancers, and targeting metabolic pathways in cancer cells has become a topic of considerable interest. However, if GSCs are indeed important for tumor control, knowledge of the metabolic state of GSCs is needed. We hypothesized that the metabolism of GSCs differs from that of their progeny. Using a unique imaging system for GSCs, we assessed the oxygen consumption rate, extracellular acidification rate, intracellular ATP levels, glucose uptake, lactate production, PKM1 and PKM2 expression, radiation sensitivity, and cell cycle duration of GSCs and their progeny in a panel of glioma cell lines. We found GSCs and progenitor cells to be less glycolytic than differentiated glioma cells. GSCs consumed less glucose and produced less lactate while maintaining higher ATP levels than their differentiated progeny. Compared with differentiated cells, GSCs were radioresistant, and this correlated with a higher mitochondrial reserve capacity. Glioma cells expressed both isoforms of pyruvate kinase, and inhibition of either glycolysis or oxidative phosphorylation had minimal effect on energy production in GSCs and progenitor cells. We conclude that GSCs rely mainly on oxidative phosphorylation. However, if challenged, they can use additional metabolic pathways. Therefore, targeting glycolysis in glioma may spare GSCs.
authors: Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Erina
authors: E
authors: Vlashi
authors: Chann
authors: C
authors: Lagadec
authors: Laurent
authors: L
authors: Vergnes
authors: Tomoo
authors: T
authors: Matsutani
authors: Kenta
authors: K
authors: Masui
authors: Maria
authors: M
authors: Poulou
authors: Ruxandra
authors: R
authors: Popescu
authors: Lorenza
authors: L
authors: Della Donna
authors: Patrick
authors: P
authors: Evers
authors: Carmen
authors: C
authors: Dekmezian
authors: Karen
authors: K
authors: Reue
authors: Heather
authors: H
authors: Christofk
authors: Paul S
authors: PS
authors: Mischel
authors: Frank
authors: F
authors: Pajonk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007773:Lactates / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography / Q000379:methods; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D046888:Tissue Array Analysis; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D007773:Lactates; D009840:Oligomycins; C484162:PSMD1 protein, human; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D046988:Proteasome Endopeptidase Complex; D005947:Glucose