title: Warburg and Crabtree effects in premalignant Barrett's esophagus cell lines with active mitochondria.
abstract: BACKGROUND
  Increased glycolysis is a hallmark of cancer metabolism, yet relatively little is known about this phenotype at premalignant stages of progression. Periodic ischemia occurs in the premalignant condition Barrett's esophagus (BE) due to tissue damage from chronic acid-bile reflux and may select for early adaptations to hypoxia, including upregulation of glycolysis.
  
  
  RESULTS
  We compared rates of glycolysis and oxidative phosphorylation in four cell lines derived from patients with BE (CP-A, CP-B, CP-C and CP-D) in response to metabolic inhibitors and changes in glucose concentration. We report that cell lines derived from patients with more advanced genetically unstable BE have up to two-fold higher glycolysis compared to a cell line derived from a patient with early genetically stable BE; however, all cell lines preserve active mitochondria. In response to the glycolytic inhibitor 2-deoxyglucose, the most glycolytic cell lines (CP-C and CP-D) had the greatest suppression of extra-cellular acidification, but were able to compensate with upregulation of oxidative phosphorylation. In addition, these cell lines showed the lowest compensatory increases in glycolysis in response to mitochondrial uncoupling by 2,4-dinitrophenol. Finally, these cell lines also upregulated their oxidative phosphorylation in response to glucose via the Crabtree effect, and demonstrate a greater range of modulation of oxygen consumption.
  
  
  CONCLUSIONS
  Our findings suggest that cells from premalignant Barrett's esophagus tissue may adapt to an ever-changing selective microenvironment through changes in energy metabolic pathways typically associated with cancer cells.
authors: Molecular and Cellular Biology Department, University of Washington, Seattle, Washington, United States of America. msuchoro@uw.edu
authors: Martin T
authors: MT
authors: Suchorolski
authors: Thomas G
authors: TG
authors: Paulson
authors: Carissa A
authors: CA
authors: Sanchez
authors: David
authors: D
authors: Hockenbery
authors: Brian J
authors: BJ
authors: Reid
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000143:Acids / Q000378:metabolism; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000494:pharmacology; D018450:Disease Progression; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005110:Extracellular Space / Q000378:metabolism; D042822:Genomic Instability / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009367:Neoplasm Staging; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D000143:Acids; D014475:Uncoupling Agents; D003847:Deoxyglucose; D019297:2,4-Dinitrophenol