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Cell. 2016 Feb 11;164(4):681-94. doi: 10.1016/j.cell.2015.12.034. Epub 2016 Feb 4.

Metabolic Heterogeneity in Human Lung Tumors.

Author information

1
Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Hadassah Medical Center, Jerusalem 91120, Israel.
4
Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
5
Clinical Research Office, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
6
Office of Animal Welfare Assurance, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
7
Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
8
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
9
Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
10
Department of Cardiovascular and Thoracic Surgery, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
11
Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
12
Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: ralph.deberardinis@utsouthwestern.edu.

Abstract

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.

Comment in

PMID:
26853473
PMCID:
PMC4752889
DOI:
10.1016/j.cell.2015.12.034
[Indexed for MEDLINE]
Free PMC Article

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