title: Fatty acid metabolites in rapidly proliferating breast cancer.
abstract: OBJECTIVE
  Breast cancers that over-express a lipoxygenase or cyclooxygenase are associated with poor survival possibly because they overproduce metabolites that alter the cancer's malignant behaviors. However, these metabolites and behaviors have not been identified. We here identify which metabolites among those that stimulate breast cancer cell proliferation in vitro are associated with rapidly proliferating breast cancer.
  
  
  METHODS
  We used selective ion monitoring-mass spectrometry to quantify in the cancer and normal breast tissue of 27 patients metabolites that stimulate (15-, 12-, 5-hydroxy-, and 5-oxo-eicosatetraenoate, 13-hydroxy-octadecaenoate [HODE]) or inhibit (prostaglandin [PG]E2 and D2) breast cancer cell proliferation. We then related their levels to each cancer's proliferation rate as defined by its Mib1 score.
  
  
  RESULTS
  13-HODE was the only metabolite strongly, significantly, and positively associated with Mib1 scores. It was similarly associated with aggressive grade and a key component of grade, mitosis, and also trended to be associated with lymph node metastasis. PGE2 and PGD2 trended to be negatively associated with these markers. No other metabolite in cancer and no metabolite in normal tissue had this profile of associations.
  
  
  CONCLUSIONS
  Our data fit a model wherein the overproduction of 13-HODE by 15-lipoxygenase-1 shortens breast cancer survival by stimulating its cells to proliferate and possibly metastasize; no other oxygenase-metabolite pathway, including cyclooxygenase-PGE2/D2 pathways, uses this specific mechanism to shorten survival.
authors: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors: Joseph T
authors: JT
authors: O'Flaherty
authors: Rhonda E
authors: RE
authors: Wooten
authors: Michael P
authors: MP
authors: Samuel
authors: Michael J
authors: MJ
authors: Thomas
authors: Edward A
authors: EA
authors: Levine
authors: L Douglas
authors: LD
authors: Case
authors: Steven A
authors: SA
authors: Akman
authors: Iris J
authors: IJ
authors: Edwards
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis
chemical_list: D014408:Biomarkers, Tumor; D005227:Fatty Acids
references: Eur J Surg Oncol. 2003 Nov;29(9):707-10
references: 14602487
references: Acta Oncol. 2008;47(4):618-32
references: 18465330
references: Ther Adv Endocrinol Metab. 2010 Apr;1(2):51-60
references: 23148150
references: Breast Cancer Res Treat. 2011 Nov;130(2):657-62
references: 21728052
references: Prostaglandins Leukot Med. 1985 Feb;17(2):199-212
references: 3920680
references: Mol Biol Med. 1984 Apr;2(2):81-8
references: 6099863
references: J Cancer Res Clin Oncol. 2003 Jul;129(7):375-82
references: 12884024
references: J Carcinog. 2006 Mar 27;5:9
references: 16566819
references: Front Biosci. 2007 Jan 01;12:1574-85
references: 17127404
references: Cancer Metastasis Rev. 2011 Dec;30(3-4):277-94
references: 22002716
references: Cancer Lett. 1996 Dec 3;109(1-2):223-30
references: 9020925
references: J Natl Cancer Inst. 2010 May 5;102(9):627-37
references: 20427430
references: Anticancer Res. 2004 Sep-Oct;24(5B):3283-8
references: 15510624
references: Prostaglandins Leukot Essent Fatty Acids. 2006 Feb;74(2):125-34
references: 16364620
references: Indian J Cancer. 2009 Jan-Mar;46(1):54-60
references: 19282568
references: J Clin Oncol. 2010 Mar 20;28(9):1467-72
references: 20159825
references: Invasion Metastasis. 1986;6(2):83-94
references: 3700014
references: Am J Physiol Regul Integr Comp Physiol. 2000 Jul;279(1):R1-8
references: 10896857
references: Prostaglandins Leukot Essent Fatty Acids. 2009 May-Jun;80(5-6):239-45
references: 19457650
references: Arch Biochem Biophys. 1998 Jan 15;349(2):376-80
references: 9448728
references: Curr Urol Rep. 2002 Jun;3(3):207-14
references: 12084190
references: FASEB J. 2001 Sep;15(11):2007-9
references: 11511519
references: Life Sci. 1995;57(12):1233-40
references: 7674812
references: Biochem Biophys Res Commun. 2002 Aug 30;296(4):942-8
references: 12200139
references: Appl Immunohistochem Mol Morphol. 2007 Sep;15(3):255-9
references: 17721268
references: Med Oncol. 2011 Sep;28(3):703-8
references: 20354817
references: Breast Cancer Res Treat. 2011 Feb;126(1):149-55
references: 20669045
references: Biochim Biophys Acta. 1994 Dec 15;1201(3):505-15
references: 7803484
references: Prostaglandins Leukot Essent Fatty Acids. 1992 Apr;45(4):319-27
references: 1603822
references: Nutr Cancer. 1996;25(3):231-40
references: 8771566
references: Br J Cancer. 1983 Nov;48(5):689-96
references: 6416285
references: Biochim Biophys Acta. 1983 Nov 1;754(1):57-71
references: 6414520
references: Pharmacoepidemiol Drug Saf. 2011 Feb;20(2):131-7
references: 21254283
references: Prostaglandins Other Lipid Mediat. 2004 Apr;73(3-4):237-47
references: 15287155
references: Biochim Biophys Acta. 2005 Oct 1;1736(3):228-36
references: 16154383
references: Cancer Lett. 1999 Jun 1;140(1-2):27-35
references: 10403538
references: Prostaglandins Leukot Essent Fatty Acids. 2003 Oct;69(4):275-81
references: 12907138
references: Clin Cancer Res. 2004 Dec 15;10(24):8275-83
references: 15623603
references: Breast Cancer Res Treat. 2012 Jun;133(2):741-51
references: 22286316
references: Adv Exp Med Biol. 1999;447:29-36
references: 10086180
references: Prostaglandins Leukot Essent Fatty Acids. 2006 Apr;74(4):235-45
references: 16556493
references: Br J Cancer. 1989 Feb;59(2):268-75
references: 2930691
references: Indian J Cancer. 2006 Oct-Dec;43(4):163-8
references: 17192687
references: Biochemistry. 2008 Jul 15;47(28):7364-75
references: 18570379