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Title: Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration

Cancer cells typically exhibit increased glycolysis and decreased mitochondrial oxidative phosphorylation, and they continue to exhibit some elevation in glycolysis even under aerobic conditions. However, it is unclear whether cancer cell lines employ a high level of glycolysis comparable to that of the original cancers from which they were derived, even if their culture conditions are changed to physiologically relevant oxygen concentrations. From three childhood acute lymphoblastic leukemia (ALL) patients we established three new pairs of cell lines in both atmospheric (20%) and physiologic (bone marrow level, 5%) oxygen concentrations. Cell lines established in 20% oxygen exhibited lower proliferation, survival, expression of glycolysis genes, glucose consumption, and lactate production. Interestingly, the effects of oxygen concentration used during cell line initiation were only partially reversible when established cell cultures were switched from one oxygen concentration to another for eight weeks. These observations indicate that ALL cell lines established at atmospheric oxygen concentration can exhibit relatively low levels of glycolysis and these levels are semi-permanent, suggesting that physiologic oxygen concentrations may be needed from the time of cell line initiation to preserve the high level of glycolysis commonly exhibited by leukemias in vivo. - Highlights: • Establishing new ALL cell lines inmore » 5% oxygen resulted in higher glycolytic expression and function. • Establishing new ALL cell lines in 5% oxygen resulted in higher proliferation and lower cell death. • The divergent metabolic phenotypes selected in 5% and 20% oxygen are semi-permanent.« less
Authors:
 [1] ;  [2] ;  [3] ;  [3] ;  [1] ;  [1] ;  [4] ;  [3] ;
  1. Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research, Division of Hematology-Oncology, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States)
  2. Department of Pathology, Keck School of Medicine, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089 (United States)
  3. Cancer Center and Departments of Cell Biology & Biochemistry, Pharmacology & Neuroscience, Internal Medicine and Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 (United States)
  4. Medical Genetics, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027 (United States)
Publication Date:
OSTI Identifier:
22462286
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 334; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABUNDANCE; AEROBIC CONDITIONS; APOPTOSIS; BONE MARROW; CELL CULTURES; CONCENTRATION RATIO; GLUCOSE; GLYCOLYSIS; IN VIVO; LACTATES; LEUKEMIA; MITOCHONDRIA; OXIDATION; OXYGEN; OXYGEN 20; PATIENTS; PHENOTYPE; PHOSPHORYLATION