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Metabolism of [U-13C]glucose in human brain tumors in vivo

Maher, Elizabeth A. ; Marin-Valencia, Isaac ; Bachoo, Robert M. ; Mashimo, Tomoyuki ; Raisanen, Jack ; Hatanpaa, Kimmo J. ; Jindal, Ashish ; Jeffrey, F. Mark ; Choi, Changho ; Madden, Christopher ; Mathews, Dana ; Pascual, Juan M. ; Mickey, Bruce E. ; Malloy, Craig R. ; DeBerardinis, Ralph J.

NMR in biomedicine, 2012-11, Vol.25 (11), p.1234-1244 [Periódico revisado por pares]

Chichester, UK: John Wiley & Sons, Ltd

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Título:
Metabolism of [U-13C]glucose in human brain tumors in vivo
Autor: Maher, Elizabeth A. ; Marin-Valencia, Isaac ; Bachoo, Robert M. ; Mashimo, Tomoyuki ; Raisanen, Jack ; Hatanpaa, Kimmo J. ; Jindal, Ashish ; Jeffrey, F. Mark ; Choi, Changho ; Madden, Christopher ; Mathews, Dana ; Pascual, Juan M. ; Mickey, Bruce E. ; Malloy, Craig R. ; DeBerardinis, Ralph J.
Assuntos: Acetyl Coenzyme A - metabolism ; Amino acids ; Blood Glucose - metabolism ; Brain Neoplasms - blood ; Brain Neoplasms - metabolism ; Brain Neoplasms - secondary ; Breast Neoplasms - pathology ; cancer ; Carbon Isotopes ; Carcinoma, Non-Small-Cell Lung - pathology ; Citric Acid Cycle ; Female ; glioblastoma ; Glioblastoma - blood ; Glioblastoma - metabolism ; glucose ; Glucose - metabolism ; glutamine ; Glycine - biosynthesis ; Glycolysis ; Humans ; metabolism ; NMR ; Oxidation-Reduction ; Warburg effect
É parte de: NMR in biomedicine, 2012-11, Vol.25 (11), p.1234-1244
Notas: istex:21675AAC2ADD92AA78C29973539325CB831BB9C5
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Descrição: Glioblastomas and brain metastases demonstrate avid uptake of 2‐[18F]fluoro‐2‐deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by 1H MRS. These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. 2‐[18F]Fluoro‐2‐deoxyglucose‐positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation relative to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid cycle is unknown. Here, we studied the metabolism of human brain tumors in situ. [U‐13 C]Glucose (uniformly labeled glucose, i.e. d‐glucose labeled with 13 C in all six carbons) was infused during surgical resection, and tumor samples were subsequently subjected to 13C NMR spectroscopy. The analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl‐coenzyme A pool was derived from blood‐borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of 13C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment. Copyright © 2012 John Wiley & Sons, Ltd. Metabolic reprogramming is a hallmark of cancer cells, yet few studies have analyzed the metabolism of human tumors in vivo. Eleven patients with solitary brain tumors were infused with [U‐13C]glucose during surgical resection, and metabolites extracted from the tumors were analyzed by 13C NMR spectroscopy. Primary tumors and brain metastases used glucose to supply many metabolic pathways, including glycolysis, the tricarboxylic acid cycle and amino acid synthesis.
Editor: Chichester, UK: John Wiley & Sons, Ltd
Idioma: Inglês

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Metabolism of [U-13C]glucose in human brain tumors in vivo

Maher, Elizabeth A. ; Marin-Valencia, Isaac ; Bachoo, Robert M. ; Mashimo, Tomoyuki ; Raisanen, Jack ; Hatanpaa, Kimmo J. ; Jindal, Ashish ; Jeffrey, F. Mark ; Choi, Changho ; Madden, Christopher ; Mathews, Dana ; Pascual, Juan M. ; Mickey, Bruce E. ; Malloy, Craig R. ; DeBerardinis, Ralph J.

Chichester, UK: John Wiley & Sons, Ltd

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