title: Metabolic Heterogeneity in Human Lung Tumors.
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.
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Christopher T
authors: CT
authors: Hensley
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Brandon
authors: B
authors: Faubert
authors: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Qing
authors: Q
authors: Yuan
authors: Hadassah Medical Center, Jerusalem 91120, Israel.
authors: Naama
authors: N
authors: Lev-Cohain
authors: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Eunsook
authors: E
authors: Jin
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Jiyeon
authors: J
authors: Kim
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Lei
authors: L
authors: Jiang
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Bookyung
authors: B
authors: Ko
authors: Clinical Research Office, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Rachael
authors: R
authors: Skelton
authors: Clinical Research Office, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Laurin
authors: L
authors: Loudat
authors: Office of Animal Welfare Assurance, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors: Michelle
authors: M
authors: Wodzak
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Claire
authors: C
authors: Klimko
authors: Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Elizabeth
authors: E
authors: McMillan
authors: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Yasmeen
authors: Y
authors: Butt
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Min
authors: M
authors: Ni
authors: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Dwight
authors: D
authors: Oliver
authors: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Jose
authors: J
authors: Torrealba
authors: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Craig R
authors: CR
authors: Malloy
authors: Department of Cardiovascular and Thoracic Surgery, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Kemp
authors: K
authors: Kernstine
authors: Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Robert E
authors: RE
authors: Lenkinski
authors: Children's Medical Center Research Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Eugene McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: ralph.deberardinis@utsouthwestern.edu.
authors: Ralph J
authors: RJ
authors: DeBerardinis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D002952:Citric Acid Cycle; D005260:Female; D006019:Glycolysis; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D059016:Tumor Microenvironment