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Cell. 2017 Oct 5;171(2):358-371.e9. doi: 10.1016/j.cell.2017.09.019.

Lactate Metabolism in Human Lung Tumors.

Author information

1
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
2
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
4
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
5
Clinical Research Unit, University of Texas Southwestern Medical Center, Dallas, TX, USA.
6
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
7
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
8
Departments of Chemical and Biomolecular Engineering and Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
9
Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
10
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ralph.deberardinis@utsouthwestern.edu.

Abstract

Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.

KEYWORDS:

Cancer metabolism; Glycolysis; Lactate; Lung cancer; Metabolic flux analysis; Monocarboxylate transport; Tricarboxylic Acid Cycle; Warburg effect

Comment in

PMID:
28985563
PMCID:
PMC5684706
[Available on 2018-10-05]
DOI:
10.1016/j.cell.2017.09.019
[Indexed for MEDLINE]

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