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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 1/2012

Open Access 01-01-2012 | Original article

Tissue expression of Toll-like receptors 2 and 4 in sporadic human colorectal cancer

Authors: Yasuhiro Nihon-Yanagi, Kensuke Terai, Takeyoshi Murano, Takayuki Matsumoto, Shinichi Okazumi

Published in: Cancer Immunology, Immunotherapy | Issue 1/2012

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Abstract

Background

Toll-like receptors (TLRs) play an important role in innate immunity by sensing a variety of pathogens and inducing acquired immunity. To test our hypothesis that dysregulation of innate immune responses acts to trigger carcinogenesis, we studied the expression of TLR2 and 4 in sporadic human colorectal cancer tissue.

Methods

In specimens of cancerous and noncancerous colorectal tissue obtained at surgery, mRNA expression levels of TLR2 and 4 were quantified by TaqMan real-time polymerase chain reaction and compared between the two types of tissue. To confirm TLR2 and TLR4 protein expression levels, immunohistochemical analysis was performed using the same samples.

Results

TLR2 mRNA expression was significantly higher in cancerous tissue than in noncancerous tissue, while TLR4 mRNA expression did not differ significantly. Immunohistochemical analysis revealed stronger staining for TLR2 in cancerous mucosal epithelial cells than in noncancerous tissue. Staining for TLR4 in the lamina propria of the mucosa was equally weakly positive in noncancerous tissue and cancerous tissue. This TLR-specific difference in expression suggested that such expression does not only reflect a local inflammatory response to cancer infiltration, i.e., if this was the case, both TLR2 and 4 expression would probably be up-regulated. Our results suggest that TLR2 expression might be involved in sporadic colorectal carcinogenesis, whereas TLR4 is not.
Literature
1.
Kuper H, Adami HO, Trichopoulos D (2000) Infections as a major preventable cause of human cancer. J Intern Med 248:171–183PubMedCrossRef
2.
3.
4.
Ernst PB, Takaishi H, Crowe SE (2001) Helicobacter pylori infection as a model for gastrointestinal immunity and chronic inflammatory disease. Dig Dis 19:104–111PubMedCrossRef
5.
Peek RM, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2:28–37PubMedCrossRef
6.
Ortega-Cava CF, Ishihara S, Rumi MAK, Kawashima K, Ishimura N, Kazumori H, Udagawa J, Kadowaki Y, Kinoshita Y (2003) Strategic compartmentalization of Toll-like receptor 4 in the mouse gut. J Immunol 170:3977–3985PubMed
7.
van der Woude CJ, Moshage H, Homan M, Klebeuker JH, Jansen PLM, van Dekken H (2003) Expression of apoptosis related proteins during malignant progression in chronic ulcerative colitis. J Clin Pathol 58:811–814CrossRef
8.
Cario E, Podolsky DK (2000) Differential alternation in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68:7010–7017PubMedCrossRef
9.
Frolova L, Drastich P, Rossmann P, Klimesova K, Tlaskalova-Hogenova H (2008) Expression of Toll-like receptor 2 (TLR2), TLR4, and CD14 in biopsy samples of patients with inflammatory bowel disease: upregulated expression of TLR2 in terminal ileum of patients with ulcerative colitis. J Histochemo Cytochemo 56:267–274CrossRef
10.
Katsanos KH, Vermeire S, Christodoulou DK, Riis L, Wolters F, Odes S, Freitas J, Hoie O, Beltrami M, Fornaciari G, Clofent J, Bodini P, Vatn M, Nunes PB, Moum B, Munkholm P, Limonard C, Stockbrugger R, Rutgeerts P, Tsianos EV (2007) Dysplasia and cancer in inflammatory bowel disease 10 years after diagnosis: results of a population-based European collaborative follow-up study. Digestion 75:113–121PubMedCrossRef
11.
Xie J, Itzkowitz SH (2008) Cancer in inflammatory bowel disease. World J Gastroenterol 14:378–389PubMedCrossRef
12.
Schmasser B, Andrulis M, Endrich S, Müller-Hermelink H, Eck M (2005) Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: An implication for interaction with Helicobacter pylori. Int J Med Microbil 295:179–185CrossRef
13.
Miyake K (2007) Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 19:3–10PubMedCrossRef
14.
Merrell MA, Ilvesaro JM, Lehtonen N, Sorsa T, Gehrs B, Rosenthal E, Chen D, Shackley B, Harris KW, Selander KS (2006) Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res 4:437–447PubMedCrossRef
15.
Garay RP, Viens P, Bauer J, Normier G, Bardou M, Jeannin J, Chiavaroli C (2007) Cancer relapse under chemotherapy: why TLR2/4 receptor abonists can help. Eur J Pharmacol 563:1–17PubMedCrossRef
16.
Zarember KA, Godowski PJ (2002) Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes. Their products, and cytokines. J Immunol 168:554–561PubMed
17.
Zhang R, Li Y, Beck PL, McCafferty D-M (2007) Toll-like receptor 4 regulates colitis-associated adenocarcinoma development in interleukin-10- deficient (IL-10−/−) mice. Biochem Soc Trans 35:1375–1376PubMedCrossRef
18.
Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397PubMedCrossRef
19.
20.
Rhee SH, Keates AC, Moyer MP, Pothoulakis C (2004) MEK is a key modulator for TLR5-induced interleukin-8 and MIP3αgene expression in non-transformed human colonic epithelial cells. J Biol Chem 24:25179–25188CrossRef
21.
Okamoto M, Sato M (2003) Toll-like receptor signaling in anti-cancer immunity. J Med Invest 50:9–24PubMed
22.
Seya T, Akazawa T, Uehori J, Matsumoto M, Azuma I, Toyoshima K (2003) Roll of Toll-like receptors and their adaptors in adjuvant immunotherapy for cancer. Anticancer Res 23:4369–4376PubMed
23.
Pidgeon GP, Harmey JH, Kay E, Da Costa M, Redmond HP, Bouchier-Hayes DJ (1999) The role of endotoxin/lipopolysaccharide in surgically induced tumour growth in a murine model of metastatic disease. Br J Cancer 81:1311–1317PubMedCrossRef
24.
Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, Hsu D, Xu R, Harpaz N, Dannenberg AJ, Subbaramaiah K, Cooper HS, Itzkowitz SH, Abreu MT (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133:1869–1881PubMedCrossRef
25.
Liu CH, Chang S, Narko K, Trifan OC, Wu M, Smith E, Haudenschild C, Lane TF, Hla T (2001) Over expression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276:18563–18569PubMedCrossRef
26.
Kelly MG, Alvero AB, Chen AR, Silasi D, Abrahams VM, Chan S, Visintin I, Rutherford T, Mor G (2006) TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res 66:3859–3868PubMedCrossRef
27.
Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ (1999) Peptidoglycan-and lipoteichoic acid-induced cell activation is mediated by Toll-like receptor 2. J Biol Chem 274:17406–17409PubMedCrossRef
28.
Underhill DM, Ozinsky A, Smith KD, Aderem A (1999) Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 96:14459–14463PubMedCrossRef
Metadata
Title
Tissue expression of Toll-like receptors 2 and 4 in sporadic human colorectal cancer
Authors
Yasuhiro Nihon-Yanagi
Kensuke Terai
Takeyoshi Murano
Takayuki Matsumoto
Shinichi Okazumi
Publication date
01-01-2012
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 1/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-1085-4

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