Lactate Metabolism in Human Lung Tumors.

Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, Li H, Huet G, Yuan Q, Wigal T, Butt Y, Ni M, Torrealba J, Oliver D, Lenkinski RE, Malloy CR, Wachsmann JW, Young JD, Kernstine K, DeBerardinis RJ
Cell. 2017 171 (2): 358-371.e9

PMID: 28985563 · PMCID: PMC5684706 · DOI:10.1016/j.cell.2017.09.019

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 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with C-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.

Copyright © 2017 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Animals Blood Chemical Analysis Carcinoma, Non-Small-Cell Lung Cell Line, Tumor Citric Acid Cycle Disease Models, Animal Female Glyceric Acids Heterografts Humans Lactic Acid Lung Neoplasms Male Mice Monocarboxylic Acid Transporters Neoplasm Transplantation Symporters

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