Metabolic Heterogeneity in Human Lung Tumors

Christopher T. Hensley; Brandon Faubert; Qing Yuan; Naama Lev-Cohain; Eunsook Jin; Jiyeon Kim; Lei Jiang; Bookyung Ko; Rachael Skelton; Laurin Loudat; Michelle Wodzak; Claire Klimko; Elizabeth McMillan; Yasmeen Butt; Min Ni; Dwight Oliver; Jose Torrealba; Craig R. Malloy; Kemp Kernstine; Robert E. Lenkinski; Ralph J. DeBerardinis

doi:10.1016/j.cell.2015.12.034

Metabolic Heterogeneity in Human Lung Tumors

Christopher T. Hensley, Brandon Faubert, Qing Yuan, Naama Lev-Cohain, Eunsook Jin, Jiyeon Kim, Lei Jiang, Bookyung Ko, Rachael Skelton, Laurin Loudat, Michelle Wodzak, Claire Klimko, Elizabeth McMillan, Yasmeen Butt, Min Ni, Dwight Oliver, Jose Torrealba, Craig R. Malloy, Kemp Kernstine, Robert E. LenkinskiRalph J. DeBerardinis

Research output: Contribution to journal › Article › peer-review

792 Scopus citations

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 ¹³C-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.

Original language	English (US)
Pages (from-to)	681-694
Number of pages	14
Journal	Cell
Volume	164
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2015.12.034
State	Published - Feb 11 2016

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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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., ... DeBerardinis, R. J. (2016). Metabolic Heterogeneity in Human Lung Tumors. Cell, 164(4), 681-694. https://doi.org/10.1016/j.cell.2015.12.034

Hensley, CT, 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, CR , Kernstine, K, Lenkinski, RE & DeBerardinis, RJ 2016, 'Metabolic Heterogeneity in Human Lung Tumors', Cell, vol. 164, no. 4, pp. 681-694. https://doi.org/10.1016/j.cell.2015.12.034

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title = "Metabolic Heterogeneity in Human Lung Tumors",

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 13C-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.",

author = "Hensley, {Christopher T.} and Brandon Faubert and Qing Yuan and Naama Lev-Cohain and Eunsook Jin and Jiyeon Kim and Lei Jiang and Bookyung Ko and Rachael Skelton and Laurin Loudat and Michelle Wodzak and Claire Klimko and Elizabeth McMillan and Yasmeen Butt and Min Ni and Dwight Oliver and Jose Torrealba and Malloy, {Craig R.} and Kemp Kernstine and Lenkinski, {Robert E.} and DeBerardinis, {Ralph J.}",

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AU - Hensley, Christopher T.

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AU - Kim, Jiyeon

AU - Jiang, Lei

AU - Ko, Bookyung

AU - Skelton, Rachael

AU - Loudat, Laurin

AU - Wodzak, Michelle

AU - Klimko, Claire

AU - McMillan, Elizabeth

AU - Butt, Yasmeen

AU - Ni, Min

AU - Oliver, Dwight

AU - Torrealba, Jose

AU - Malloy, Craig R.

AU - Kernstine, Kemp

AU - Lenkinski, Robert E.

AU - DeBerardinis, Ralph J.

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N2 - 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 13C-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.

AB - 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 13C-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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Metabolic Heterogeneity in Human Lung Tumors

Abstract

ASJC Scopus subject areas

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