Skip to main content
SpringerLink
Log in

Study of the Expression of Toll-Like Receptors in Different Histological Types of Colorectal Polyps and Their Relationship with Colorectal Cancer

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Purpose

Dysregulation of toll-like receptors (TLR) signaling can result in chronic inflammatory and over-exuberant repair responses. The aim of this study was to investigate the expression and clinical relevance of TLR in colorectal polyps.

Methods

The expression levels of six TLR were analyzed in 70 patients with different histological types of colorectal polyps, 38 of which developed colorectal carcinoma (CC). These analyses were performed by real-time polymerase chain reaction, western blot, and immunohistochemistry.

Results

TLR9 expression was higher in hyperplastic or adenomatous polyps compared to other polyp types. Hyperplastic polyps also showed increased TLR7 levels compared to the other polyp types. TLR7 expression was lower in both hyperplastic and tubulovillous adenoma polyps from patients who developed CC. TLR9 expression was decreased in hyperplastic and villous polyps from patients who developed CC.

Conclusions

Our findings suggest a possible protective role of TLR expression against malignant transformation in the colorectal mucosa. TLR may represent a pathological marker of CC risk in colorectal polyps. The role of these factors in the pathology of colorectal polyps deserves further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Bujanda L, Cosme A, Gil I, Arenas-Mirave JI. Malignant colorectal polyps. World J Gastroenterol. 2010;16:3103–11.

    Article  PubMed  Google Scholar 

  3. Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale—update based on new evidence. Gastroenterology. 2003;124:544–60.

    Article  PubMed  Google Scholar 

  4. Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, et al. Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006;145:880–6.

    PubMed  Google Scholar 

  5. Markowitz AJ, Winawer SJ. Screening and surveillance for colorectal carcinoma. Hematol Oncol Clin North Am. 1997;11:579–608.

    Article  PubMed  CAS  Google Scholar 

  6. Kawai T, Akira S. TLR signaling. Cell Death Differ. 2006;13:816–25.

    Article  PubMed  CAS  Google Scholar 

  7. Xiao H, Gulen MF, Qin J, Yao J, Bulek K, Kish D, et al. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis. Immunity. 2007;26:461–75.

    Article  PubMed  CAS  Google Scholar 

  8. Abreu MT. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol. 2010;10:131–44.

    Article  PubMed  CAS  Google Scholar 

  9. Lowe EL, Crother TR, Rabizadeh S, Hu B, Wang H, Chen S, et al. Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer. PLoS One. 2010;5:e13027.

    Article  PubMed  Google Scholar 

  10. Tsan MF. Toll-like receptors, inflammation and cancer. Semin Cancer Biol. 2006;16:32–7.

    Article  PubMed  CAS  Google Scholar 

  11. Shi SR, Liu C, Balgley BM, Lee C, Taylor CR. Protein extraction from formalin-fixed, paraffin-embedded tissue sections: quality evaluation by mass spectrometry. J Histochem Cytochem. 2006;54:739–43.

    Article  PubMed  CAS  Google Scholar 

  12. Zucchini N, Bessou G, Traub S, Robbins SH, Uematsu S, Akira S, et al. Cutting edge: overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection. J Immunol. 2008;180:5799–803.

    PubMed  CAS  Google Scholar 

  13. Coelho TR, Almeida L, Lazo PA. JC virus in the pathogenesis of colorectal cancer, an etiological agent or another component in a multistep process? Virol J. 2010;7:42.

    Article  PubMed  Google Scholar 

  14. Rollison DE, Helzlsouer KJ, Lee JH, Fulp W, Clipp S, Hoffman-Bolton JA, et al. Prospective study of JC virus seroreactivity and the development of colorectal cancers and adenomas. Cancer Epidemiol Biomarkers Prev. 2009;18:1515–23.

    Article  PubMed  CAS  Google Scholar 

  15. Shibolet O, Podolsky DK. TLRs in the gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1469–73.

    Article  PubMed  CAS  Google Scholar 

  16. Wang D, Lou J, Ouyang C, Chen W, Liu Y, Liu X, et al. Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane. Proc Natl Acad Sci U S A. 2010;107:13806–11.

    Article  PubMed  CAS  Google Scholar 

  17. Niedzielska I, Niedzielski Z, Tkacz M, Orawczyk T, Ziaja K, Starzewski J, et al. Toll-like receptors and the tendency of normal mucous membrane to transform to polyp or colorectal cancer. J Physiol Pharmacol. 2009;60 Suppl 1:65–71.

    PubMed  Google Scholar 

  18. Chen XZ, Mao XH, Zhu KJ, Jin N, Ye J, Cen JP, et al. Toll like receptor agonists augment HPV 11 E7-specific T cell responses by modulating monocyte-derived dendritic cells. Arch Dermatol Res. 2010;302:57–65.

    Article  PubMed  CAS  Google Scholar 

  19. Sun S, Rao NL, Venable J, Thurmond R, Karlsson L. TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007;6:223–35.

    Article  PubMed  CAS  Google Scholar 

  20. Pawar RD, Ramanjaneyulu A, Kulkarni OP, Lech M, Segerer S, Anders HJ. Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus. J Am Soc Nephrol. 2007;18:1721–31.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang Y, Lee AS, Shameli A, Geng X, Finegood D, Santamaria P, et al. TLR9 blockade inhibits activation of diabetogenic CD8+ T cells and delays autoimmune diabetes. J Immunol. 2010;184:5645–53.

    Article  PubMed  CAS  Google Scholar 

  22. Liljegren A, Lindblom A, Rotstein S, Nilsson B, Rubio C, Jaramillo E. Prevalence and incidence of hyperplastic polyps and adenomas in familial colorectal cancer: correlation between the two types of colon polyps. Gut. 2003;52:1140–7.

    Article  PubMed  CAS  Google Scholar 

  23. Lim HK, Lee KH, Kim SY, Kim KJ, Kim B, Lee H, et al. Does the amount of tagged stool and fluid significantly affect the radiation exposure in low-dose CT colonography performed with an automatic exposure control? Eur Radiol. 2011;21:345–52.

    Article  PubMed  Google Scholar 

  24. Omata F, Deshpande G, Tokuda Y, Takahashi O, Ohde S, Carr-Locke DL, et al. Meta-analysis: somatostatin or its long-acting analogue, octreotide, for prophylaxis against post-ERCP pancreatitis. J Gastroenterol. 2010;45:885–95.

    Article  PubMed  CAS  Google Scholar 

  25. Vizoso FJ, Gonzalez LO, Corte MD, Rodriguez JC, Vazquez J, Lamelas ML, et al. Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer. 2007;96:903–11.

    Article  PubMed  CAS  Google Scholar 

  26. Escaff S, Fernandez JM, Gonzalez LO, Suarez A, Gonzalez-Reyes S, Gonzalez JM, et al. Study of matrix metalloproteinases and their inhibitors in prostate cancer. Br J Cancer. 2010;102:922–9.

    Article  PubMed  CAS  Google Scholar 

  27. Altadill A, Rodriguez M, Gonzalez LO, Junquera S, Corte MD, Gonzalez-Dieguez ML, et al. Liver expression of matrix metalloproteases and their inhibitors in hepatocellular carcinoma. Dig Liver Dis. 2009;41:740–8.

    Article  PubMed  CAS  Google Scholar 

  28. Gonzalez-Reyes S, Fernandez JM, Gonzalez LO, Aguirre A, Suarez A, Gonzalez JM, et al. Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol Immunother. 2011;60:217–26.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from Fondo de Inversión Sanitaria del Instituto Carlos III (FIS-PI070306 and EXPTE: PI070306) and FICEMU.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Unidad de Investigación, Hospital de Jove, Avenida Eduardo Castro s/n, C.P. 33290, Gijón, Asturias, Spain

    Noemí Eiró, Lucía González, Luis O. González, Alejandro Andicoechea, María Fernández-Díaz, Antonio Altadill & Francisco J. Vizoso

  2. Servicio de Anatomía Patológica, Hospital de Jove, Gijón, Spain

    Luis O. González

  3. Servicio de Cirugía General, Hospital de Jove, Gijón, Spain

    Alejandro Andicoechea & Francisco J. Vizoso

  4. Servicio de Medicina Interna, Hospital de Jove, Gijón, Spain

    Antonio Altadill

Authors
  1. Noemí Eiró
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucía González
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luis O. González
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alejandro Andicoechea
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María Fernández-Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Altadill
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francisco J. Vizoso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francisco J. Vizoso.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eiró, N., González, L., González, L.O. et al. Study of the Expression of Toll-Like Receptors in Different Histological Types of Colorectal Polyps and Their Relationship with Colorectal Cancer. J Clin Immunol 32, 848–854 (2012). https://doi.org/10.1007/s10875-012-9666-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-012-9666-3

Keywords

Search

Navigation