Metabolism of [U‐ 13 C]glucose in human brain tumors in vivo
Open accessAbstract
Glioblastomas and brain metastases demonstrate avid uptake of 2-[(18) F]fluoro-2-deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by (1) H 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-[(18) F]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 (13) C 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 (13) C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment.
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Tracing glucose-derived carbons in human patients and mouse models of glioblastoma and NSCLC reveals that in these contexts the principal source for TCA cycle intermediates is glucose, not glutamine.
“In fact, tracing the fate of glucose-derived carbons in human patients and in mouse models of glioblastoma and non-small cell lung carcinoma (NSCLC) reveals that at least in these tumorigenic contexts, the principal source for the TCA cycle intermediates is not glutamine, but glucose (Maher et al., 2012; Marin-Valencia et al., 2012; Sellers et al., 2015).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Maher et al., 2012
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- Authors
- Maher, E. A., Marin‐Valencia, I., Bachoo, R. M., Mashimo, T., Raisanen, J., Hatanpaa, K. J., Jindal, A., Jeffrey, F. M., Choi, C., Madden, C., Mathews, D., Pascual, J. M., Mickey, B. E., Malloy, C. R., & DeBerardinis, R. J.
- Affiliations
- Harold C. Simmons Comprehensive Cancer Center (US)
- The University of Texas Southwestern Medical Center (US)
- VA North Texas Health Care System (US)
- Corresponding author
- Maher, Elizabeth A.
- DeBerardinis, Ralph J.
- ORCID
- Venue
- NMR in Biomedicine
- Publisher
- Wiley
- Published
- 2012-03-15
- Volume
- 25
- Issue
- 11
- Pages
- 1234-1244
- ISSN
- 0952-3480 (ISSN-L)
- 1099-1492
- PMC
- PMC3406255
- OpenAlex
- W2114805483
- Cited by
- 341
- References
- 49
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 21 · 2023: 19 · 2022: 28 · 2021: 41 · 2020: 28 · 2019: 30 · 2018: 22 · 2017: 18 · 2016: 34 · 2015: 33 · 2014: 14 · 2013: 11 · 2012: 4
- FWCI
- 6.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NMR in Biomedicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- National Cancer Institute (R01CA154843, R01CA157996)
- National Institute of Neurological Disorders and Stroke (RC1NS0760675, RC1NS070675)
- National Center for Research Resources (P41RR002584, RR‐02584)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- brain tumors, glioblastoma, brain metastases, glucose metabolism, Warburg effect, lactic acid production, TCA cycle, pyruvate dehydrogenase, anaplerosis, acetyl-CoA, tumor bioenergetics, metabolic reprogramming
- MeSH terms
- Acetyl Coenzyme A, Blood Glucose, Brain Neoplasms, Breast Neoplasms, Carbon Isotopes, Carcinoma, Non-Small-Cell Lung, Citric Acid Cycle, Female, Glioblastoma, Glucose, Glycine, Glycolysis, Humans, Oxidation-Reduction
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