Skip to main content
SpringerLink
Log in

Serum Interleukin-33 Levels in Patients with Gastric Cancer

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines, and it is closely related to IL-18, one of the best characterized members of the IL-1 family. It’s been demonstrated that elevated levels of IL-18 are involved in a wide variety of tumors, especially in gastric cancer.

Aims

The purpose of this study was to determine the correlations between serum IL-33 levels and the clinicopathologic features in gastric cancer patients.

Methods

Serum samples were collected from 68 patients with gastric cancer and 57 controls. Serum IL-33 levels were measured by ELISA. Classical tumor markers of CEA and CA19-9 levels were routinely detected by chemiluminescence immunoassay. Western blot analysis was used to detect IL-33 expression in gastric cancer tissue samples and cell lines. The relationship between serum levels of IL-33 and clinical characteristics in patients was analyzed.

Results

IL-33 levels in the serum of gastric cancer patients were significantly elevated in comparison with that of healthy volunteers. Furthermore, higher serum levels of IL-33 in gastric cancer patients were found to correlate with several poor prognostic factors like depth of invasion, distant metastasis and advanced stage (stage III/IV). On the other hand, serum IL-33 levels did not correlate with CEA and CA19-9. The expression of IL-33 protein was upregulated in carcinoma tissues in comparison with matched normal tissues, and no statistically significant difference was found between the four gastric cancer cell lines and human gastric epithelial cell line GES-1.

Conclusions

Serum IL-33 may be a useful biomarker for predicting the prognosis of gastric cancer.

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. Pisani P, Parkin DM, Ferlay J. Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden. Int J Cancer. 1993;55:891–903.

    Article  PubMed  CAS  Google Scholar 

  2. Terry MB, Gaudet MM, Gammon MD. The epidemiology of gastric cancer. Semin Radiat Oncol. 2002;12:111–127.

    Article  PubMed  Google Scholar 

  3. Ikeguchi M, Hatada T, Yamamoto M, et al. Serum interleukin-6 and -10 levels in patients with gastric cancer. Gastric Cancer. 2009;12:95–100.

    Article  PubMed  CAS  Google Scholar 

  4. Seguchi T, Yokokawa K, Sugao H, Nakano E, Sonoda T, Okuyama A. Interleukin-6 activity in urine and serum in patients with bladder carcinoma. J Urol. 1992;148:791–794.

    PubMed  CAS  Google Scholar 

  5. Fortis C, Foppoli M, Gianotti L, et al. Increased interleukin-10 serum levels in patients with solid tumors. Cancer Lett. 1996;104:1–5.

    Article  PubMed  CAS  Google Scholar 

  6. Kang JS, Bae SY, Kim HR, et al. Interleukin-18 increases metastasis and immune escape of stomach cancer via the downregulation of CD70 and maintenance of CD44. Carcinogenesis. 2009;30:1987–1996.

    Article  PubMed  CAS  Google Scholar 

  7. Thong-Ngam D, Tangkijvanich P, Lerknimitr R, Mahachai V, Theamboonlers A, Poovorawan Y. Diagnostic role of serum interleukin-18 in gastric cancer patients. World J Gastroenterol. 2006;12:4473–4477.

    PubMed  CAS  Google Scholar 

  8. Haghshenas MR, Hosseini SV, Mahmoudi M, Saberi-Firozi M, Farjadian S, Ghaderi A. IL-18 serum level and IL-18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers. J Gastroenterol Hepatol. 2009;24:1119–1122.

    Article  PubMed  CAS  Google Scholar 

  9. Carriere V, Roussel L, Ortega N, et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci USA. 2007;104:282–287.

    Article  PubMed  CAS  Google Scholar 

  10. Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–490.

    Article  PubMed  CAS  Google Scholar 

  11. Onda H, Kasuya H, Takakura K, et al. Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 1999;19:1279–1288.

    Article  PubMed  CAS  Google Scholar 

  12. Dinarello CA. Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol. 1998;16:457–499.

    Article  PubMed  CAS  Google Scholar 

  13. Park H, Byun D, Kim TS, et al. Enhanced IL-18 expression in common skin tumors. Immunol Lett. 2001;79:215–219.

    Article  PubMed  CAS  Google Scholar 

  14. Eissa SA, Zaki SA, El-Maghraby SM, Kadry DY. Importance of serum IL-18 and RANTES as markers for breast carcinoma progression. J Egypt Natl Canc Inst. 2005;17:51–55.

    PubMed  Google Scholar 

  15. Merendino RA, Gangemi S, Ruello A, et al. Serum levels of interleukin-18 and sICAM-1 in patients affected by breast cancer: preliminary considerations. Int J Biol Markers. 2001;16:126–129.

    PubMed  CAS  Google Scholar 

  16. Lee S, Kang J, Cho M, et al. Profiling of transcripts and proteins modulated by K-ras oncogene in the lung tissues of K-ras transgenic mice by omics approaches. Int J Oncol. 2009;34:161–172.

    PubMed  CAS  Google Scholar 

  17. Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’? PLoS One. 2008;3:e3331.

    Article  PubMed  Google Scholar 

  18. Masamune A, Watanabe T, Kikuta K, Satoh K, Kanno A, Shimosegawa T. Nuclear expression of interleukin-33 in pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2010;299:G821–G832.

    Article  PubMed  CAS  Google Scholar 

  19. Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008;7:827–840.

    Article  PubMed  CAS  Google Scholar 

  20. Trajkovic V, Sweet MJ, Xu D. T1/ST2–an IL-1 receptor-like modulator of immune responses. Cytokine Growth Factor Rev. 2004;15:87–95.

    Article  PubMed  CAS  Google Scholar 

  21. Gayle MA, Slack JL, Bonnert TP, et al. Cloning of a putative ligand for the T1/ST2 receptor. J Biol Chem. 1996;271:5784–5789.

    Article  PubMed  CAS  Google Scholar 

  22. Kumar S, Minnich MD, Young PR. ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1. J Biol Chem. 1995;270:27905–27913.

    Article  PubMed  CAS  Google Scholar 

  23. Ali S, Huber M, Kollewe C, Bischoff SC, Falk W, Martin MU. IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells. Proc Natl Acad Sci USA. 2007;104:18660–18665.

    Article  PubMed  CAS  Google Scholar 

  24. Chackerian AA, Oldham ER, Murphy EE, Schmitz J, Pflanz S, Kastelein RA. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol. 2007;179:2551–2555.

    PubMed  CAS  Google Scholar 

  25. De Vita F, Orditura M, Galizia G, et al. Serum interleukin-10 levels in patients with advanced gastrointestinal malignancies. Cancer. 1999;86:1936–1943.

    Article  PubMed  Google Scholar 

  26. Sharma A, Rajappa M, Saxena A, Sharma M. Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix. Int J Gynecol Cancer. 2007;17:879–885.

    Article  PubMed  CAS  Google Scholar 

  27. Choi YS, Choi HJ, Min JK, et al. Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood. 2009;114:3117–3126.

    Article  PubMed  CAS  Google Scholar 

  28. Becker CE, O’Neill LA. Inflammasomes in inflammatory disorders: the role of TLRs and their interactions with NLRs. Semin Immunopathol. 2007;29:239–248.

    Article  PubMed  CAS  Google Scholar 

  29. Kawabata T, Ichikura T, Majima T, et al. Preoperative serum interleukin-18 level as a postoperative prognostic marker in patients with gastric carcinoma. Cancer. 2001;92:2050–2055.

    Article  PubMed  CAS  Google Scholar 

  30. Iikura M, Suto H, Kajiwara N, et al. IL-33 can promote survival, adhesion and cytokine production in human mast cells. Lab Invest. 2007;87:971–978.

    Article  PubMed  CAS  Google Scholar 

  31. Salminen A, Kaarniranta K. Glycolysis links p53 function with NF-kappaB signaling: impact on cancer and aging process. J Cell Physiol. 2010;224:1–6.

    PubMed  CAS  Google Scholar 

  32. Mancino A, Lawrence T. Nuclear factor-kappaB and tumor-associated macrophages. Clin Cancer Res. 2010;16:784–789.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Zhongyin Yang, Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin No.2 Road, 200025, Shanghai, People’s Republic of China

    Pinghu Sun, Shuiping Tu, Wenjie Dong, Xiaoguang Qi & Yunlin Wu

  2. Department of Gastroenterology, Changhai Hospital of Second Military Medical University, 168 Changhai Road, 200433, Shanghai, People’s Republic of China

    Qiwen Ben

Authors
  1. Pinghu Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiwen Ben
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuiping Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenjie Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoguang Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunlin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yunlin Wu.

Additional information

Pinghu Sun and Qiwen Ben contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, P., Ben, Q., Tu, S. et al. Serum Interleukin-33 Levels in Patients with Gastric Cancer. Dig Dis Sci 56, 3596–3601 (2011). https://doi.org/10.1007/s10620-011-1760-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-011-1760-5

Keywords

Search

Navigation