Metabolic heterogeneity in human lung tumors
Open accessAbstract
Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. Here, we assessed the impact of these factors on human NSCLC metabolism in vivo using intraoperative (13)C-glucose infusions in nine NSCLC patients to compare metabolism between tumors and benign lung. While enhanced glycolysis and glucose oxidation were common among these tumors, we observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source. Moreover, metabolically heterogeneous regions were identified within and between tumors, and surprisingly, our data suggested potential contributions of non-glucose nutrients in well-perfused tumor areas. Our findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature.
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In non-small cell lung cancer patients, intraoperative isotopically labeled glucose infusions showed a higher contribution of glucose carbon to TCA intermediates than to glycolytic intermediates, leading the authors to conclude that lactate could serve as an anaplerotic substrate.
“Intraoperative isotopically-labeled glucose infusions performed on non-small cell lung cancer patients revealed higher contribution of glucose carbon to TCA intermediates than glycolytic intermediates in tumors, leading the authors to conclude that lactate could serve as an anaplerotic substrate in this context as well (Hensley et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Hensley et al., 2016
Glutamine tracing studies have demonstrated that in some tumor tissues glutamine contributes minimally to TCA cycle intermediates, and those cancers can be resistant to glutaminase inhibition.
“Glutamine tracing studies have demonstrated that in some tumor tissues, glutamine contributes minimally to TCA cycle intermediates, and those cancers can be resistant to glutaminase inhibition (Davidson et al., 2016; Hensley et al., 2016; Marin-Valencia et al., 2012; Sellers et al., 2015; Tardito et al., 2015).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Hensley et al., 2016
Glucose tracing studies indicate that tumor cells in highly perfused locations rely mainly on glucose, whereas those in less perfused regions depend on other carbon sources.
“Glucose tracing studies stipulate that tumor cells in highly perfused locations rely mainly on glucose, whereas those in less perfused regions depend on other carbon sources [237].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [237]
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- Authors
- Hensley, C. T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., Wodzak, M., Klimko, C., McMillan, E., Butt, Y., Ni, M., Oliver, D., Torrealba, J., Malloy, C. R., Kernstine, K., Lenkinski, R. E., & DeBerardinis, R. J.
- Affiliations
- Children's Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- DeBerardinis, Ralph J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 164
- Issue
- 4
- Pages
- 681-694
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4752889
- OpenAlex
- W2258066491
- Cited by
- 1,138
- References
- 33
- Citations by year
- 2026: 87 · 2025: 96 · 2024: 103 · 2023: 116 · 2022: 110 · 2021: 161 · 2020: 118 · 2019: 123 · 2018: 90 · 2017: 85 · 2016: 45
- FWCI
- 47.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001105)
- National Cancer Institute ((P50-CA70907, P50CA070907, CA157996-04S1, R01CA157996)
- National Institute of General Medical Sciences (T32GM008203)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099289)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015908)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- non-small cell lung cancer, tumor metabolic heterogeneity, tumor microenvironment, tumor glucose metabolism, glycolysis, glucose oxidation, lactate oxidation, tumor perfusion
- MeSH terms
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Citric Acid Cycle, Female, Glycolysis, Humans, Lung Neoplasms, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Tumor Microenvironment
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