title: Genetic deletion of 5-lipoxygenase increases tumor-infiltrating macrophages in Apc(Δ468) mice.
abstract: BACKGROUND
  The role of 5-lipoxygenase (5-LO) in colon cancer is unknown. Tumor-infiltrating macrophages, neutrophils, and mast cells have been shown to play important roles in colon tumorigenesis and are dependent on 5-LO for function.
  
  
  METHODS
  Utilizing the APC(Δ468) polyposis model, we performed 5-LO gene knockouts and evaluated the subsequent changes in macrophage, neutrophil, and mast cell density at the tumor site. The proliferative and degranulation capacities of 5-LO-deficient mast cells were also measured, quantifying thymidine incorporation and β-hexosaminidase release, respectively.
  
  
  RESULTS
  APC(Δ468)/5LO(-/-) mice displayed increased tumor-infiltrating macrophages and decreased neutrophils at the polyp site. In vitro, mast cells deficient for 5-LO proliferated at a diminished rate while mast cell degranulation was unchanged.
  
  
  CONCLUSIONS
  We provide evidence suggesting that 5-LO deficiency has differential effects on the infiltration of macrophages and neutrophils in adenomatous polyps, increasing and decreasing infiltration of these cells, respectively. Our observations are consistent with a protective role for tumor-infiltrating macrophages in the initiation of polyp formation. The mechanisms through which 5-LO deficiency negatively affects these cells are under investigation.
  
  
  CONCLUSIONS
  These results provide evidence that 5-LO plays an important role in tumorigenesis and further indicate that 5-LO-selective inhibitors can be investigated as potential therapeutic agents for colorectal polyposis and cancer.
authors.affiliation: Department of Surgery, Mount Sinai Hospital, University of Illinois College of Medicine, 1500 S California Ave, Chicago, IL 60608, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Cheon
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Strouch
authors.forename: Seth B
authors.initials: SB
authors.lastname: Krantz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heiferman
authors.forename: David J
authors.initials: DJ
authors.lastname: Bentrem
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D003111:Colonic Polyps / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology / Q000473:pathology
chemical_list: D001094:Arachidonate 5-Lipoxygenase
references.citation: Clin Cancer Res. 2008 Oct 15;14(20):6525-30
references.pmid: 18927292
references.citation: J Immunol. 2006 May 1;176(9):5513-8
references.pmid: 16622020
references.citation: Cancer Res. 1994 May 1;54(9):2462-7
references.pmid: 8162595
references.citation: J Allergy Clin Immunol. 2005 Feb;115(2):316-22
references.pmid: 15696087
references.citation: Cancer Res. 2000 May 15;60(10):2632-5
references.pmid: 10825134
references.citation: Clin Cancer Res. 2007 Mar 1;13(5):1472-9
references.pmid: 17332291
references.citation: Cancer Res. 1996 Oct 15;56(20):4625-9
references.pmid: 8840975
references.citation: Gastroenterology. 2003 Jan;124(1):57-70
references.pmid: 12512030
references.citation: Cancer Res. 2011 Mar 1;71(5):1627-36
references.pmid: 21216893
references.citation: J Clin Pathol. 1997 Aug;50(8):669-73
references.pmid: 9301551
references.citation: J Mammary Gland Biol Neoplasia. 2002 Apr;7(2):177-89
references.pmid: 12463738
references.citation: World J Gastroenterol. 2005 Feb 28;11(8):1210-4
references.pmid: 15754407
references.citation: J Immunol. 1996 Jan 1;156(1):42-7
references.pmid: 8598491
references.citation: Int J Exp Pathol. 2008 Dec;89(6):466-75
references.pmid: 19134056
references.citation: J Exp Med. 2001 Nov 5;194(9):1243-52
references.pmid: 11696590
references.citation: Anticancer Res. 2002 Nov-Dec;22(6C):4291-6
references.pmid: 12553072
references.citation: J Clin Invest. 2008 Feb;118(2):560-70
references.pmid: 18219394
references.citation: Oncogene. 2002 Jul 18;21(31):4728-38
references.pmid: 12101411
references.citation: Clin Exp Allergy. 2003 Oct;33(10):1380-8
references.pmid: 14519144
references.citation: Nature. 1980 Jul 17;286(5770):264-5
references.pmid: 6250050
references.citation: J Immunol. 1993 Apr 15;150(8 Pt 1):3478-86
references.pmid: 8385686
references.citation: Am J Respir Crit Care Med. 2001 Jan;163(1):226-33
references.pmid: 11208650
references.citation: J Allergy Clin Immunol. 2006 Oct;118(4):837-43
references.pmid: 17030235
references.citation: J Immunol. 2006 Sep 1;177(5):2755-9
references.pmid: 16920908
references.citation: Clin Cancer Res. 1999 May;5(5):1107-13
references.pmid: 10353745
references.citation: Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2291-7
references.pmid: 18768495
references.citation: Nat Immunol. 2005 Aug;6(8):800-9
references.pmid: 16025118
references.citation: J Leukoc Biol. 2000 Dec;68(6):897-902
references.pmid: 11129658
references.citation: J Pathol. 2000 Oct;192(2):150-8
references.pmid: 11004690
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6430-5
references.pmid: 20308560
references.citation: Oncol Rep. 2003 Mar-Apr;10(2):309-13
references.pmid: 12579264
references.citation: J Pathol. 2000 Mar;190(4):430-6
references.pmid: 10699991
references.citation: Gastroenterology. 2000 Oct;119(4):1007-18
references.pmid: 11040187