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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.

DOI:10.1016/j.cell.2015.12.034
PMID:26853473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4752889/
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。

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Nature. 2025 Sep 3. doi: 10.1038/s41586-025-09460-7.
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Emerging role of the TCA cycle and its metabolites in lung disease.三羧酸循环及其代谢产物在肺部疾病中的新作用
Front Physiol. 2025 Aug 15;16:1621013. doi: 10.3389/fphys.2025.1621013. eCollection 2025.
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RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.RANBP9和RANBP10在调节非小细胞肺癌增殖方面相互协作。

本文引用的文献

1
Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells.代谢可塑性维持丙酮酸脱氢酶缺乏细胞的增殖。
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Metabolic pathways promoting cancer cell survival and growth.促进癌细胞存活和生长的代谢途径。
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A roadmap for interpreting (13)C metabolite labeling patterns from cells.解读细胞中(13)C代谢物标记模式的路线图。
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Lactate Metabolism in Health and Disease.健康与疾病中的乳酸代谢
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Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.氧化代谢与糖酵解代谢:它们在癌症中的相互调节与失调
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Conservation and divergence of metabolic phenotypes between patient tumours and matched xenografts.患者肿瘤与其匹配的异种移植瘤之间代谢表型的保守性与差异性。
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Glyoxalase 1 gene expression in various types of cancer cells immunopathology: a pan-cancer analysis study.乙二醛酶1基因在各类癌细胞中的表达免疫病理学:一项泛癌分析研究
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10
Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.向骨骼发送信号:肿瘤衍生的细胞外囊泡如何协调前转移微环境的形成和骨骼定植
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Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.丙酮酸羧化酶对非小细胞肺癌的增殖至关重要。
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Acetate is a bioenergetic substrate for human glioblastoma and brain metastases.醋酸盐是人类胶质母细胞瘤和脑转移瘤的生物能量底物。
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