title: Preservation of high glycolytic phenotype by establishing new acute lymphoblastic leukemia cell lines at physiologic oxygen concentration.
abstract: 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.
authors.affiliation: 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, USA. Electronic address: msheard@chla.usc.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sheard
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089, USA. Electronic address: mattghent@gmail.com.
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Ghent
authors.affiliation: 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, USA. Electronic address: dcabral14@gmail.com.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cabral
authors.affiliation: 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, USA. Electronic address: joannebarnhart@gmail.com.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: 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, USA. Electronic address: khangaldian@yahoo.com.
authors.forename: Vazgen
authors.initials: V
authors.lastname: Khankaldyyan
authors.affiliation: 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, USA. Electronic address: lingyun.ji@med.usc.edu.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ji
authors.affiliation: Medical Genetics, Children׳s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA. Electronic address: swu@chla.usc.edu.
authors.forename: Samuel Q
authors.initials: SQ
authors.lastname: Wu
authors.affiliation: 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, USA. Electronic address: min.kang@ttuhsc.edu.
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
authors.affiliation: 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, USA. Electronic address: rsposto@chla.usc.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.affiliation: Department of Pediatrics, Keck School of Medicine, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089, USA. Electronic address: sasgharzadeh@chla.usc.edu.
authors.forename: Shahab
authors.initials: S
authors.lastname: Asgharzadeh
authors.affiliation: 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, USA. Electronic address: patrick.reynolds@ttuhsc.edu.
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003124:Colorimetry; D020869:Gene Expression Profiling; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010100:Oxygen / Q000378:metabolism*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005947:Glucose; D010100:Oxygen
keywords: Glycolysis; Oxygen; Proliferation
references.citation: Vox Sang. 1995;68(4):210-4
references.pmid: 7660638
references.citation: Cancer Res. 1982 Apr;42(4):1331-6
references.pmid: 7037175
references.citation: Mol Carcinog. 2013 May;52(5):329-37
references.pmid: 22228080
references.citation: J Natl Cancer Inst. 2006 Sep 6;98(17):1193-203
references.pmid: 16954472
references.citation: Nat Rev Cancer. 2004 Nov;4(11):891-9
references.pmid: 15516961
references.citation: Nature. 2013 Aug 8;500(7461):207-11
references.pmid: 23925245
references.citation: Leuk Res. 2006 Jan;30(1):81-9
references.pmid: 15998540
references.citation: Curr Protoc Immunol. 2002 Aug;Chapter 4:Unit 4.9
references.pmid: 18432883
references.citation: Methods Mol Med. 2005;110:87-100
references.pmid: 15901930
references.citation: J Immunol Methods. 1999 Aug 31;228(1-2):13-21
references.pmid: 10556538
references.citation: Cytometry. 1997 Sep 1;29(1):50-7
references.pmid: 9298811
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Cytometry B Clin Cytom. 2005 Jan;63(1):47-55
references.pmid: 15624203
references.citation: FASEB J. 2005 Mar;19(3):434-6
references.pmid: 15637111
references.citation: Mutat Res. 2003 Oct 29;531(1-2):231-51
references.pmid: 14637258
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4547-52
references.pmid: 17360561
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: J Clin Invest. 2008 Dec;118(12):3930-42
references.pmid: 19033663
references.citation: Science. 2011 Dec 2;334(6060):1278-83
references.pmid: 22052977
references.citation: Leuk Res. 2000 Mar;24(3):255-62
references.pmid: 10739008
references.citation: Clin Chem. 1997 Oct;43(10):1843-9
references.pmid: 9342002
references.citation: Cancer Res. 1984 Dec;44(12 Pt 1):5657-60
references.pmid: 6437672
references.citation: Cancer Lett. 2006 Jun 8;237(1):10-21
references.pmid: 16002209
references.citation: Blood. 1978 Oct;52(4):712-8
references.pmid: 278631
references.citation: J Immunol Methods. 2003 Jul;278(1-2):145-55
references.pmid: 12957403
references.citation: J Cell Biochem. 2011 Mar;112(3):735-44
references.pmid: 21328446
references.citation: Leukemia. 1993 Nov;7(11):1865-74
references.pmid: 8231254
references.citation: J Pediatr Hematol Oncol. 2003 Jul;25(7):520-5
references.pmid: 12847317
references.citation: Biochem Biophys Res Commun. 2002 Mar 8;291(4):806-12
references.pmid: 11866437
references.citation: Blood. 2007 Aug 15;110(4):1271-7
references.pmid: 17456722
references.citation: Leukemia. 2006 Oct;20(10):1731-7
references.pmid: 17041637
references.citation: Head Neck. 1999 Mar;21(2):146-53
references.pmid: 10091983
references.citation: Oncogene. 2005 Sep 1;24(38):5914-22
references.pmid: 15897868
references.citation: Mol Cancer Ther. 2007 Mar;6(3):886-97
references.pmid: 17363483
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31-6
references.pmid: 11134512