Glucose metabolism in human gliomas: Correspondence ofin situ andin vitro metabolic rates and altered energy metabolism

Abstract

The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by fluorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I-III gliomas had a glucose consumption rate of 2-3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by 18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measured in situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the glioma-derived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomas in situ and (2) are significantly altered in several aspects of their glycolytic metabolism.

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer

“…We suggest that the metabolic mechanism by which moderate DR inhibits CT-2A brain tumour growth involves a failure to utilise alternative energy substrates. Most tumours including primary brain tumours actively consume glucose and are largely dependent on glycolysis for energy (Warberg, 1956;Galarraga et al, 1986;Mies et al, 1990;Oudard et al, 1997;Roslin et al, 2003). Mitochondrial defects and an inability to metabolise ketone bodies are thought to be responsible for the dependence of tumour cells on glycolytic energy (Warberg, 1956;Fredericks and Ramsey, 1978;Pedersen, 1978;Tisdale and Brennan, 1983;Lichtor and Dohrmann, 1986;Oudard et al, 1997;John, 2001).…”

Hypoxia-inducible Factor 1 Activation by Aerobic Glycolysis Implicates the Warburg Effect in Carcinogenesis

“…Cancer cells maintain high aerobic glycolytic rates and produce high levels of lactate and pyruvate (1). This phenomenon was first described in cancer more than seven decades ago and is known historically as the Warburg effect (2,3).…”

“…Hypoxia is another common feature of many solid cancers and has been linked to malignant transformation, metastasis, and treatment resistance (11). The adaptation of cancer cells to hypoxia is mediated via hypoxia-inducible Factor 1 (HIF-1), 1 a key transcription factor that upregulates a series of genes involved in glycolytic energy metabolism, angiogenesis, cell survival, and erythropoiesis. Included among these genes are vascular endothelial growth factor (VEGF), erythropoietin (EPO), glucose transporters (GLUT), and several glycolytic enzymes (12,13).…”

Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer

“…Most normal mammalian cells achieve this level of useable energy through respiration, whereas tumor cells achieve this level through a combination of respiration and glycolysis (2,5). Indeed, elevated glycolysis is the metabolic hallmark of nearly all tumors, including brain tumors, and is the basis for tumor imaging using labeled glucose analogs (5)(6)(7)(8). Much controversy has surrounded the Warburg theory, however, largely over issues regarding the Pasture effect and aerobic glycolysis (9)(10)(11)(12)(13)(14).…”