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Molecular Physiology & Biophysics

Lactate Metabolism in Human Lung Tumors.

AUTHORS

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 10 5; 171(2). 358-371.e9

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 highfluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients withC-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.

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 highfluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients withC-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.

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