Suppr超能文献

人类肺部肿瘤中的代谢异质性

Metabolic Heterogeneity in Human Lung Tumors.

作者信息

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

机构信息

Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

出版信息

Cell. 2016 Feb 11;164(4):681-94. doi: 10.1016/j.cell.2015.12.034. Epub 2016 Feb 4.

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 (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.

摘要

非小细胞肺癌(NSCLC)在影响培养细胞代谢的遗传和环境参数方面具有异质性。在此,我们通过对9例NSCLC患者术中输注(13)C-葡萄糖,评估了这些因素对人NSCLC体内代谢的影响,以比较肿瘤与良性肺组织之间的代谢情况。虽然这些肿瘤中增强的糖酵解和葡萄糖氧化很常见,但我们观察到每个肿瘤中都有多种营养物质氧化的证据,包括乳酸作为潜在的碳源。此外,在肿瘤内部和肿瘤之间发现了代谢异质性区域,令人惊讶的是,我们的数据表明非葡萄糖营养物质在灌注良好的肿瘤区域有潜在贡献。我们的研究结果不仅证明了体内肿瘤代谢的异质性,还突出了微环境对这一特征的强大影响。

相似文献

1
Metabolic Heterogeneity in Human Lung Tumors.
Cell. 2016 Feb 11;164(4):681-94. doi: 10.1016/j.cell.2015.12.034. Epub 2016 Feb 4.
3
Glucose metabolism provide distinct prosurvival benefits to non-small cell lung carcinomas.
Biochem Biophys Res Commun. 2015 May 8;460(3):572-7. doi: 10.1016/j.bbrc.2015.03.071. Epub 2015 Mar 26.
4
Relationship between primary lesion metabolic parameters and clinical stage in lung cancer.
Rev Esp Med Nucl Imagen Mol. 2013 Nov-Dec;32(6):357-63. doi: 10.1016/j.remn.2013.03.008. Epub 2013 Jun 6.
5
New positron emission tomography derived parameters as predictive factors for recurrence in resected stage I non-small cell lung cancer.
Eur J Surg Oncol. 2013 Nov;39(11):1254-61. doi: 10.1016/j.ejso.2013.07.092. Epub 2013 Aug 13.
6
Lactate Metabolism in Human Lung Tumors.
Cell. 2017 Oct 5;171(2):358-371.e9. doi: 10.1016/j.cell.2017.09.019.
8
Multifunctional profiling of non-small cell lung cancer using 18F-FDG PET/CT and volume perfusion CT.
J Nucl Med. 2012 Apr;53(4):521-9. doi: 10.2967/jnumed.111.097865. Epub 2012 Mar 13.
9
Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis.
J Thorac Oncol. 2010 Aug;5(8):1120-9. doi: 10.1097/JTO.0b013e3181e2c1ff.
10
Noninvasive evaluation of microscopic tumor extensions using standardized uptake value and metabolic tumor volume in non-small-cell lung cancer.
Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):960-6. doi: 10.1016/j.ijrobp.2010.10.064. Epub 2011 Mar 26.

引用本文的文献

1
Rewiring of cortical glucose metabolism fuels human brain cancer growth.
Nature. 2025 Sep 3. doi: 10.1038/s41586-025-09460-7.
2
Emerging role of the TCA cycle and its metabolites in lung disease.
Front Physiol. 2025 Aug 15;16:1621013. doi: 10.3389/fphys.2025.1621013. eCollection 2025.
3
RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.
J Exp Clin Cancer Res. 2025 Aug 29;44(1):259. doi: 10.1186/s13046-025-03491-8.
4
Lactate Metabolism in Health and Disease.
Adv Exp Med Biol. 2025;1478:573-613. doi: 10.1007/978-3-031-88361-3_24.
7
"Molecular pigeon" network of lncRNA and miRNA: decoding metabolic reprogramming in patients with lung cancer.
Front Oncol. 2025 Jul 17;15:1578927. doi: 10.3389/fonc.2025.1578927. eCollection 2025.
9
Glyoxalase 1 gene expression in various types of cancer cells immunopathology: a pan-cancer analysis study.
Front Oncol. 2025 Jul 14;15:1610886. doi: 10.3389/fonc.2025.1610886. eCollection 2025.

本文引用的文献

1
Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells.
Cancer Metab. 2015 Jun 29;3:7. doi: 10.1186/s40170-015-0134-4. eCollection 2015.
2
Metabolic pathways promoting cancer cell survival and growth.
Nat Cell Biol. 2015 Apr;17(4):351-9. doi: 10.1038/ncb3124. Epub 2015 Mar 16.
3
A roadmap for interpreting (13)C metabolite labeling patterns from cells.
Curr Opin Biotechnol. 2015 Aug;34:189-201. doi: 10.1016/j.copbio.2015.02.003. Epub 2015 Feb 28.
4
Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.
J Clin Invest. 2015 Feb;125(2):687-98. doi: 10.1172/JCI72873. Epub 2015 Jan 20.
5
Acetate is a bioenergetic substrate for human glioblastoma and brain metastases.
Cell. 2014 Dec 18;159(7):1603-14. doi: 10.1016/j.cell.2014.11.025.
7
Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.
PLoS One. 2014 Sep 16;9(9):e105038. doi: 10.1371/journal.pone.0105038. eCollection 2014.
8
MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis.
J Clin Invest. 2014 Jan;124(1):398-412. doi: 10.1172/JCI71180. Epub 2013 Dec 9.
9
Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer.
PLoS One. 2013 Sep 12;8(9):e75154. doi: 10.1371/journal.pone.0075154. eCollection 2013.
10
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.
Nature. 2013 Apr 4;496(7443):101-5. doi: 10.1038/nature12040. Epub 2013 Mar 27.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验