title: BLT2 is expressed in PanINs, IPMNs, pancreatic cancer and stimulates tumour cell proliferation.
abstract: Pancreatic cancer has an abysmal prognosis. Targets for early detection, prevention and therapy are desperately needed. Inflammatory pathways have an important impact on tumour growth and progression. Expression of BLT2 (the second leukotriene B(4) receptor) was investigated by real-time RT-PCR and immunohistochemistry. Cell proliferation was studied after stable transfection with BLT2, after treatment with siRNA and Compound A as an agonist. BLT2 is expressed in all pancreatic cancer cell lines. Results from real-time RT-PCR revealed significant overexpression of BLT2 in malignant intraductal papillary mucinous neoplasias (IPMNs) and pancreatic adenocarcinoma. Intense staining was evident in IPMNs, infiltrating tumour cells and advanced pancreatic intraepithelial neoplasias (PanINs) but not in normal ductal cells. Overexpression of BLT2 as well as stimulation of Colo357, Panc-1 and AsPC1 cells with Compound A caused a significant increase in tumour cell proliferation, an effect reversed after siRNA treatment. This study demonstrates for the first time the expression of BLT2 in the pancreas and overexpression in pancreatic cancers and malignant IPMNs in particular. Upregulation of BLT2 is already evident in precursor lesions (PanINs, IPMNs). Overexpression of this receptor leads to significant growth stimulation. Therefore, we suggest BLT2 as a new target for chemoprevention and therapy for pancreatic cancer.
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany. rene.hennig@chir.med.tu-muenchen.de
authors.forename: R
authors.initials: R
authors.lastname: Hennig
authors.forename: T
authors.initials: T
authors.lastname: Osman
authors.forename: I
authors.initials: I
authors.lastname: Esposito
authors.forename: N
authors.initials: N
authors.lastname: Giese
authors.forename: S M
authors.initials: SM
authors.lastname: Rao
authors.forename: X-Z
authors.initials: XZ
authors.lastname: Ding
authors.forename: W-G
authors.initials: WG
authors.lastname: Tong
authors.forename: M W
authors.initials: MW
authors.lastname: Büchler
authors.forename: T
authors.initials: T
authors.lastname: Yokomizo
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: T E
authors.initials: TE
authors.lastname: Adrian
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D007975:Leukotriene B4 / Q000378:metabolism; D008024:Ligands; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism; D034741:RNA, Small Interfering; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C485878:LTB4R2 protein, human; D008024:Ligands; D034741:RNA, Small Interfering; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4
references.citation: J Epidemiol. 1998 Mar;8(1):52-9
references.pmid: 9575696
references.citation: J Epidemiol. 2005 Jun;15 Suppl 2:S157-67
references.pmid: 16127228
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):6913-8
references.pmid: 16624877
references.citation: Am J Surg Pathol. 2001 May;25(5):579-86
references.pmid: 11342768
references.citation: Am J Pathol. 2002 Aug;161(2):421-8
references.pmid: 12163367
references.citation: Mol Cancer. 2003 Jan 07;2:10
references.pmid: 12575899
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G7-17
references.pmid: 15194558
references.citation: Breast Cancer. 1997 Mar 25;4(1):7-16
references.pmid: 11091570
references.citation: Rev Gastroenterol Disord. 2002;2 Suppl 2:S2-8
references.pmid: 12478238
references.citation: J Natl Cancer Inst. 2002 Nov 20;94(22):1671
references.pmid: 12441321
references.citation: J Exp Med. 2000 Aug 7;192(3):421-32
references.pmid: 10934230
references.citation: Cancer Res. 2002 Aug 1;62(15):4199-201
references.pmid: 12154018
references.citation: Lancet Oncol. 2002 Sep;3(9):518
references.pmid: 12217773
references.citation: J Immunol. 2006 Sep 1;177(5):3439-47
references.pmid: 16920986
references.citation: Cancer Causes Control. 2007 Aug;18(6):603-12
references.pmid: 17401636
references.citation: J Cell Sci. 2002 May 1;115(Pt 9):1883-93
references.pmid: 11956320
references.citation: Proc Natl Acad Sci U S A. 1984 Apr;81(7):2199-202
references.pmid: 6326112
references.citation: Oncogene. 2004 Dec 9;23(57):9259-68
references.pmid: 15489890
references.citation: Biochem Biophys Res Commun. 2006 Sep 22;348(2):606-11
references.pmid: 16889750
references.citation: Exp Mol Med. 2005 Feb 28;37(1):45-50
references.pmid: 15761251
references.citation: N Engl J Med. 2004 Mar 18;350(12):1200-10
references.pmid: 15028824
references.citation: Food Chem Toxicol. 1999 Sep-Oct;37(9-10):981-4
references.pmid: 10541454
references.citation: Oncology (Williston Park). 2002 Jun;16(6):725-34; discussion 734, 736-8, 740, 743
references.pmid: 12088296
references.citation: J Clin Oncol. 2005 Jul 10;23(20):4532-7
references.pmid: 16002844
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Aug;287(2):G315-9
references.pmid: 15246966
references.citation: Curr Probl Cancer. 1996 Sep-Oct;20(5):281-328
references.pmid: 8902402
references.citation: Cancer Res. 2005 Feb 1;65(3):732-42
references.pmid: 15705869
references.citation: Expert Opin Investig Drugs. 2007 Dec;16(12):1909-20
references.pmid: 18042000
references.citation: Clin Cancer Res. 2002 Oct;8(10):3232-42
references.pmid: 12374694
references.citation: Gastroenterology. 2003 Jan;124(1):57-70
references.pmid: 12512030
references.citation: J Biol Chem. 2002 Mar 8;277(10):8572-8
references.pmid: 11756405
references.citation: Mutat Res. 1999 Jul 15;443(1-2):111-27
references.pmid: 10415435
references.citation: Pancreas. 1998 Apr;16(3):233-7
references.pmid: 9548660
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2006 Apr;74(4):223-33
references.pmid: 16556492
references.citation: Oncogene. 2006 Oct 26;25(50):6660-5
references.pmid: 16715140
references.citation: Am J Clin Pathol. 2002 Aug;118(2):194-201
references.pmid: 12162677
references.citation: Anticancer Drugs. 2007 Jun;18(5):535-41
references.pmid: 17414622
references.citation: J Immunol. 2006 May 15;176(10):6254-61
references.pmid: 16670336
references.citation: CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30
references.pmid: 16514137
references.citation: Arch Biochem Biophys. 2001 Jan 15;385(2):231-41
references.pmid: 11368003
references.citation: Br J Cancer. 2005 Apr 25;92(8):1372-81
references.pmid: 15812554
references.citation: Adv Exp Med Biol. 2003;525:201-4
references.pmid: 12751768
references.citation: Clin Exp Allergy. 2000 Jun;30 Suppl 1:22-7
references.pmid: 10849470
references.citation: Free Radic Biol Med. 2008 Feb 15;44(4):624-34
references.pmid: 18082638
references.citation: J Biol Chem. 2005 Jul 1;280(26):24816-23
references.pmid: 15866883
references.citation: Clin Cancer Res. 2000 Aug;6(8):2969-72
references.pmid: 10955772
references.citation: Nature. 1997 Jun 5;387(6633):620-4
references.pmid: 9177352