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