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 journalArticle

344 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 languageEnglish (US)
Pages (from-to)681-694
Number of pages14
JournalCell
Volume164
Issue number4
DOIs
StatePublished - Feb 11 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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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