Metabolic Heterogeneity in Human Lung Tumors

被引：831

作者：

Hensley, Christopher T. ^{[1
]}

Faubert, Brandon ^{[1
]}

Yuan, Qing ^{[2
]}

Lev-Cohain, Naama ^{[11
]}

Jin, Eunsook ^{[3
,4
]}

Kim, Jiyeon ^{[1
]}

Jiang, Lei ^{[1
]}

Ko, Bookyung ^{[1
]}

Skelton, Rachael ^{[5
]}

Loudat, Laurin ^{[5
]}

Wodzak, Michelle ^{[12
]}

Klimko, Claire ^{[1
]}

McMillan, Elizabeth ^{[6
]}

Butt, Yasmeen ^{[7
]}

Ni, Min ^{[1
]}

Oliver, Dwight ^{[7
]}

Torrealba, Jose ^{[7
]}

Malloy, Craig R. ^{[2
,3
,4
]}

Kernstine, Kemp ^{[8
]}

Lenkinski, Robert E. ^{[2
,3
]}

DeBerardinis, Ralph J. ^{[1
,9
,10
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Res Inst, Childrens Med Ctr, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[5] Univ Texas SW Med Ctr Dallas, Clin Res Off, Dallas, TX 75390 USA

[6] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA

[7] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

[8] Univ Texas SW Med Ctr Dallas, Dept Cardiovasc & Thorac Surg, Dallas, TX 75390 USA

[9] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA

[10] Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA

[11] Hadassah Med Ctr, IL-91120 Jerusalem, Israel

[12] Univ Oklahoma, Hlth Sci Ctr, Off Anim Welf Assurance, Oklahoma City, OK 73104 USA

来源：

CELL | 2016年 / 164卷 / 04期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

PYRUVATE-CARBOXYLASE; CANCER; GROWTH; GLYCOLYSIS; PATHWAYS; MRI;

D O I：

10.1016/j.cell.2015.12.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 13 C-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.

引用

页码：681 / 694

页数：14

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