Metabolic heterogeneity in human lung tumors

By C. Hensley, B. Faubert, Qing Yuan, N. Lev-Cohain, Eunsook S. Jin, Jiyeon Kim, Lei Jiang, Bookyung Ko, R. Skelton, Laurin Loudat and 11 more. Cell, 2016

995 citations recorded by the source corpus.

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 intra-operative 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7c6575a668244cf79e6393f4a53e01180bf26448

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Citations in the corpus

The Acidic Tumor Microenvironment as a Driver of Cancer. (2019, result): “Thus, the heterogeneity of tumor acidosis is in line with the well-recognized metabolic heterogeneity of tumors (66, 67) and may also support a symbiotic relationship between tumor cells”
Targeting Metabolism for Cancer Therapy (2017, background): “…performed on non-small cell lung cancer patients revealed higher contribution of glucose carbon to TCA intermediates than glycolytic intermediates in tumors, leading the authors to conclude that lactate could serve as an anaplerotic substrate in this context as well (Hensley et al., 2016).”
Understanding the intersections between metabolism and cancer biology (2017, neutral): “Recent data indicate that PDH is active and required by some tumors (Davidson et al., 2016b; Hensley et al., 2016), tempering hope that further activating the enzyme will be therapeutically useful.”
From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, neutral): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
The Science and Translation of Lactate Shuttle Theory. (2018, background): “That cancer cells respire with lactate drawn from the TME is an important realization in itself (Hensley et al., 2016; Hussien and Brooks, 2011), but also oxidative lactate disposal within tumors sets up the concentration gradient necessary for lactate shuttling.”
Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation (2018, background): “On the other hand, there is an increasing evidence of the role of oncogenes and tumour suppressors in the regulation of nutrient metabolism [187].”
Mitochondrial metabolism and cancer (2017, background): “Progressing malignancies acquire a high degree of phenotypic and metabolic plasticity as they establish functional interactions with non-transformed components of the tumor microenvironment [114-116].”
Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer (2016, background): “While all of the tumor models examined contain a high proportion of cancer cells relative to other cell types, differences in glucose metabolism are observed in different regions of human cancers (Hensley et al., 2016).”
Metabolic Instruction of Immunity (2017, positive): “Using 13C-labeled glucose, Hensley and colleagues traced the fate of glucose within healthy lung tissue and tumors of patients with non-small lung cell carcinoma and found that even within a single tumor, heterogeneity in glucose utilization exists (Hensley et al., 2016).”
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches (2019, background): “Consistent with the proposed “tumor metabolic symbiosis,” metabolically heterogeneous regions within and between tumors were identified, which are regulated by TME conditions such as hypoxia in the center of the tumor and better oxygenated regions in the periphery (113) (Figure 2).”
Metabolic reprogramming and cancer progression (2020, background): “In human lung cancer, infusing patients with (13)C-glucose during surgical resection of their tumors revealed marked regional metabolic heterogeneity despite the presence of truncal mutations in multiple regions (58, 59).”
Fundamentals of cancer metabolism (2016, methodology): “Enhanced glucose oxidation involving both PC and pyruvate dehydrogenase (PDH) was demonstrated in a separate cohort of non–small cell lung tumors, inwhich formal analysis of metabolic fluxes was used to complement measurements of (13)C labeling (197).”