Tumor Biology

, Volume 37, Issue 2, pp 1609–1615 | Cite as

Distinctive expression pattern of interleukin-17 cytokine family members in colorectal cancer

  • Ahmed Al-Samadi
  • Shirin Moossavi
  • Abdelhakim Salem
  • Masoud Sotoudeh
  • Sarianna M. Tuovinen
  • Yrjö T. Konttinen
  • Tuula Salo
  • Faraz Bishehsari
Original Article

Abstract

Colorectal cancer (CRC) is one of the most common cancers in both genders. Even though interleukin (IL)-17A was shown to play an important role in intestinal tumourigenesis and CRC, other IL-17 family members were not studied well. We therefore studied the expression of IL-17 cytokine family members in CRC. Ten healthy colons and ten CRC mucosa were immunostained for IL-17B, IL-17C, IL-17E, and IL-17F, and their receptors IL-17RA, IL-17RB, and IL-17RC. Double immunofluorescence staining of the CRC mucosa was done for IL-17B with markers of neutrophils, endothelial cells, macrophages, T cells, mast cells, or fibroblasts. While IL-17B was increased in CRC with a strong presence both in the epithelial and stromal compartments, IL-17C showed different expression depending on the grade of differentiation and IL-17E remained unchanged. In contrast, IL-17F was decreased in CRC compared to healthy control. Colon epithelial cells stained positive for IL-17RA, IL-17RB, and IL-17RC in both healthy control and CRC. Neutrophils were the main source of IL-17B in the stroma. IL-17 family members demonstrated distinct expression patterns in CRC, suggesting a differential role exerted by each member in colon carcinogenesis.

Keywords

IL-17 Colorectal cancer IL-17B Neutrophil 

Notes

Acknowledgments

This work was supported by the Finska Läkaresällskapet, the Paulo Foundation, the Sigrid Jusélius Foundation, the Finnish Dental Society Apollonia, and the Digestive Disease Research Institute.

Conflicts of interest

None

Supplementary material

13277_2015_3941_MOESM1_ESM.docx (20.9 mb)
ESM 1 (DOCX 21364 kb)

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. 2001;91(4):854–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Pappu R, Ramirez-Carrozzi V, Sambandam A. The interleukin-17 cytokine family: critical players in host defence and inflammatory diseases. Immunology. 2011;134(1):8–16.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pappu R, Ramirez-Carrozzi V, Ota N, Ouyang W, Hu Y. The IL-17 family cytokines in immunity and disease. J Clin Immunol. 2010;30(2):185–95.CrossRefPubMedGoogle Scholar
  5. 5.
    Wu D, Wu P, Huang Q, Liu Y, Ye J, Huang J. Interleukin-17: a promoter in colorectal cancer progression. Clin Dev Immunol. 2013;2013:436307.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Wu P, Wu D, Ni C, Ye J, Chen W, Hu G, et al. γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer. Immunity. 2014;40(5):785–800.Google Scholar
  7. 7.
    Wang K, Kim MK, Di Caro G, Wong J, Shalapour S, Wan J, et al. Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis. Immunity. 2014;41(6):1052–63.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wagsater D, Lofgren S, Hugander A, Dimberg J. Expression of interleukin-17 in human colorectal cancer. Anticancer Res. 2006;26(6B):4213–6.PubMedGoogle Scholar
  9. 9.
    Wang J, Xu K, Wu J, Luo C, Li Y, Wu X, et al. The changes of Th17 cells and the related cytokines in the progression of human colorectal cancers. BMC Cancer. 2012;12:418.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012;491(7423):254–8.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, Th2, Treg, Th17) in patients with colorectal cancer. Cancer Res. 2011;71(4):1263–71.Google Scholar
  13. 13.
    Liu J, Duan Y, Cheng X, Chen X, Xie W, Long H, et al. IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun. 2011;407(2):348–54.CrossRefPubMedGoogle Scholar
  14. 14.
    Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA. 2010;107(12):5540–4.Google Scholar
  15. 15.
    Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–22.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hayata K, Iwahashi M, Ojima T, Katsuda M, Iida T, Nakamori M, et al. Inhibition of IL-17A in tumor microenvironment augments cytotoxicity of tumor-infiltrating lymphocytes in tumor-bearing mice. PLoS One. 2013;8(1), e53131.Google Scholar
  17. 17.
    Kryczek I, Wei S, Szeliga W, Vatan L, Zou W. Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood. 2009;114(2):357–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Bishehsari F, Mahdavinia M, Malekzadeh R, Verginelli F, Catalano T, Sotoudeh M, et al. Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin. Ann Oncol. 2006;17 Suppl 7:vii91–6.PubMedGoogle Scholar
  19. 19.
    Al-Samadi A, Kouri VP, Salem A, Ainola M, Kaivosoja E, Barreto G, et al. IL-17C and its receptor IL-17RA/IL-17RE identify human oral epithelial cell as an inflammatory cell in recurrent aphthous ulcer. J Oral Pathol Med. 2014;43(2):117–24.Google Scholar
  20. 20.
    Johnston A, Fritz Y, Dawes SM, Diaconu D, Al-Attar PM, Guzman AM, et al. Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol. 2013;190(5):2252–62.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001;15(6):985–95.CrossRefPubMedGoogle Scholar
  22. 22.
    Kouri VP, Olkkonen J, Ainola M, Li TF, Bjorkman L, Konttinen YT, et al. Neutrophils produce interleukin-17B in rheumatoid synovial tissue. Rheumatology (Oxford). 2014;53(1):39–47.CrossRefGoogle Scholar
  23. 23.
    Li H, Chen J, Huang A, Stinson J, Heldens S, Foster J, et al. Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci USA. 2000;97(2):773–8.Google Scholar
  24. 24.
    Yagi Y, Andoh A, Inatomi O, Tsujikawa T, Fujiyama Y. Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts. J Gastroenterol. 2007;42(9):746–53.CrossRefPubMedGoogle Scholar
  25. 25.
    Huang CK, Yang CY, Jeng YM, Chen CL, Wu HH, Chang YC, et al. Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-κB-mediated antiapoptotic pathway. Oncogene. 2014;33(23):2968–77.Google Scholar
  26. 26.
    Tazzyman S, Niaz H, Murdoch C. Neutrophil-mediated tumour angiogenesis: subversion of immune responses to promote tumour growth. Semin Cancer Biol. 2013;23(3):149–58.CrossRefPubMedGoogle Scholar
  27. 27.
    Tecchio C, Cassatella MA. Neutrophil-derived cytokines involved in physiological and pathological angiogenesis. Chem Immunol Allergy. 2014;99:123–37.CrossRefPubMedGoogle Scholar
  28. 28.
    Song X, Gao H, Lin Y, Yao Y, Zhu S, Wang J, et al. Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis. Immunity. 2014;40(1):140–52.CrossRefPubMedGoogle Scholar
  29. 29.
    Caruso R, Sarra M, Stolfi C, Rizzo A, Fina D, Fantini MC, et al. Interleukin-25 inhibits interleukin-12 production and Th1 cell-driven inflammation in the gut. Gastroenterology. 2009;136(7):2270–9.CrossRefPubMedGoogle Scholar
  30. 30.
    McHenga SS, Wang D, Li C, Shan F, Lu C. Inhibitory effect of recombinant IL-25 on the development of dextran sulfate sodium-induced experimental colitis in mice. Cell Mol Immunol. 2008;5(6):425–31.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Rizzo A, Monteleone I, Fina D, Stolfi C, Caruso R, Fantini MC, et al. Inhibition of colitis by IL-25 associates with induction of alternatively activated macrophages. Inflamm Bowel Dis. 2012;18(3):449–59.CrossRefPubMedGoogle Scholar
  32. 32.
    McHenga SS, Wang D, Janneh FM, Feng Y, Zhang P, Li Z, et al. Differential dose effects of recombinant IL-25 on the development of dextran sulfate sodium-induced colitis. Inflamm Res. 2010;59(10):879–87.CrossRefPubMedGoogle Scholar
  33. 33.
    Camelo A, Barlow JL, Drynan LF, Neill DR, Ballantyne SJ, Wong SH, et al. Blocking IL-25 signalling protects against gut inflammation in a type-2 model of colitis by suppressing nuocyte and NKT derived IL-13. J Gastroenterol. 2012;47(11):1198–211.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Tong Z, Yang XO, Yan H, Liu W, Niu X, Shi Y, et al. A protective role by interleukin-17F in colon tumorigenesis. PLoS One. 2012;7(4), e34959.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Xie Y, Sheng W, Xiang J, Ye Z, Yang J. Interleukin-17F suppresses hepatocarcinoma cell growth via inhibition of tumor angiogenesis. Cancer Invest. 2010;28(6):598–607.Google Scholar
  36. 36.
    Yamaguchi Y, Fujio K, Shoda H, Okamoto A, Tsuno NH, Takahashi K, et al. IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. J Immunol. 2007;179(10):7128–36.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ahmed Al-Samadi
    • 1
    • 2
  • Shirin Moossavi
    • 3
  • Abdelhakim Salem
    • 1
  • Masoud Sotoudeh
    • 4
  • Sarianna M. Tuovinen
    • 1
  • Yrjö T. Konttinen
    • 1
    • 5
    • 6
  • Tuula Salo
    • 2
  • Faraz Bishehsari
    • 7
  1. 1.Department of Medicine, Institute of Clinical MedicineUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of Oral and Maxillofacial DiseasesUniversity of HelsinkiHelsinkiFinland
  3. 3.Digestive Oncology Research Center; Digestive Disease Research InstituteTehran University of Medical Sciences, Shariati HospitalTehranIran
  4. 4.Pathology DepartmentTehran University of Medical SciencesTehranIran
  5. 5.Department of MedicineHelsinki University Central HospitalHelsinkiFinland
  6. 6.ORTON Orthopedic Hospital of the Invalid FoundationHelsinkiFinland
  7. 7.Division of Digestive DiseasesRush University Medical CenterChicagoUSA

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