Metabolic Heterogeneity in Human Lung Tumors

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 meta...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2016-02, Vol.164 (4), p.681-694
Main Authors: Hensley, Christopher T., Faubert, Brandon, Yuan, Qing, Lev-Cohain, Naama, Jin, Eunsook, Kim, Jiyeon, Jiang, Lei, Ko, Bookyung, Skelton, Rachael, Loudat, Laurin, Wodzak, Michelle, Klimko, Claire, McMillan, Elizabeth, Butt, Yasmeen, Ni, Min, Oliver, Dwight, Torrealba, Jose, Malloy, Craig R., Kernstine, Kemp, Lenkinski, Robert E., DeBerardinis, Ralph J.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung - blood supply
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Citric Acid Cycle
Female
Glycolysis
Humans
Lung Neoplasms - blood supply
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Magnetic Resonance Imaging
Male
Middle Aged
Positron-Emission Tomography
Tumor Microenvironment
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •Human NSCLC tumors have enhanced glucose oxidation relative to adjacent benign lung•NSCLC tumors oxidize multiple types of nutrients in vivo•Glucose metabolism is heterogeneous within and between human tumors Preoperative multimodality imaging combined with intraoperative 13C-glucose infusions reveals significant heterogeneity in tumor metabolism between patients and within individual tumors.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2015.12.034