Skip to main content
SpringerLink
Log in

Role of interleukin 1 beta in esophageal squamous cell carcinoma

  • Original Article
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Interleukin (IL)-1 beta has been reported to be a marker of shorter survival in gastric and colorectal adenocarcinoma. In the present study, we examined the potential role and prognostic value of IL-1 beta in esophageal squamous cell carcinoma (SCC). Human esophageal SCC cell line, CE81T, was selected for cellular and animal experiments, in which biological changes after experimental manipulation of IL-1 beta signaling were explored, including tumor growth, invasion capacity, and the sensitivity to treatment. Moreover, 147 esophageal SCC samples were analyzed using immunohistochemical staining to correlate the expression of IL-1 beta with clinical outcome. Our data revealed that IL-1 beta was significantly overexpressed both at mRNA and protein levels in cancer specimens compared to nonmalignant tissues. When IL-1 beta signaling was blocked, tumor growth, invasion ability, and treatment resistance were attenuated. Activation of NF-kappa B, increase of E2-EPF ubiquitin carrier protein and subsequent epithelial–mesenchymal transition might be the underlying mechanisms of the more aggressive tumor growth in IL-1 beta-positive esophageal cancer. The immunochemistry findings indicate that positivity staining of IL-1 beta correlated significantly with higher clinical stage, lower response rate to concurrent chemoradiotherapy (CCRT), and higher recurrence rate after curative treatment. Moreover, IL-1 beta was a significant predictor of survival in patients undergoing surgical intervention or definite CCRT. In conclusion, IL-1 beta is significantly linked to poor prognosis for patients with esophageal cancer and may be a promising molecular target for therapeutic intervention for esophageal SCC.

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
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

SCC:

Squamous cell carcinoma

UCP:

E2-EPF ubiquitin carrier protein

EMT:

Epithelial–mesenchymal transition

VHL:

Von Hippel–Lindau gene

HIF-1α:

Hypoxia-inducible factor-1α

VEGF:

Vascular endothelial growth factor

References

  1. Enzinger PC, Mayer RJ (2003) Esophageal cancer. N Engl J Med 349:2241–2252

    Article  PubMed  CAS  Google Scholar 

  2. Bedenne L, Michel P, Bouche O, Milan C, Mariette C et al (2007) Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25:1160–1168

    Article  PubMed  CAS  Google Scholar 

  3. Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H et al (2001) Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg 234:360–367, discussion 368–369

    Article  PubMed  CAS  Google Scholar 

  4. Rohatgi PR, Swisher SG, Correa AM, Wu TT, Liao Z et al (2006) Histologic subtypes as determinants of outcome in esophageal carcinoma patients with pathologic complete response after preoperative chemoradiotherapy. Cancer 106:552–558

    Article  PubMed  Google Scholar 

  5. Siewert JR, Ott K (2007) Are squamous and adenocarcinomas of the esophagus the same disease? Semin Radiat Oncol 17:38–44

    Article  PubMed  Google Scholar 

  6. Wu X, Gu J, Wu TT, Swisher SG, Liao Z et al (2006) Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol 24:3789–3798

    Article  PubMed  CAS  Google Scholar 

  7. Nozoe T, Saeki H, Sugimachi K (2001) Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg 182:197–201

    Article  PubMed  CAS  Google Scholar 

  8. Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ (2003) Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer 89:1028–1030

    Article  PubMed  CAS  Google Scholar 

  9. Gelin J, Moldawer LL, Lonnroth C, Sherry B, Chizzonite R et al (1991) Role of endogenous tumor necrosis factor alpha and interleukin one for experimental tumor growth and the development of cancer cachexia. Cancer Res 51:415–421

    PubMed  CAS  Google Scholar 

  10. Strassmann G, Fong M, Freter CE, Windsor S, D’Alessandro F et al (1993) Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo. J Clin Invest 92:2152–2159

    Article  PubMed  CAS  Google Scholar 

  11. Smyth MJ, Cretney E, Kershaw MH et al (2004) Cytokines in cancer immunity and immunotherapy. Immunol Rev 202:275–293

    Article  PubMed  CAS  Google Scholar 

  12. Abdel-Latif MM, Duggan S, Reynolds JV, Kelleher D (2009) Inflammation and esophageal carcinogenesis. Curr Opin Pharmacol 9:396–404

    Article  PubMed  CAS  Google Scholar 

  13. Weber A, Wasiliew P, Kracht M (2010) Interleukin-1 (IL-1) pathway. Sci Signal 3:cm1

    Article  PubMed  Google Scholar 

  14. Arlt A, Vorndamm J, Muerkoster S, Yu H, Schmidt WE et al (2002) Autocrine production of interleukin 1beta confers constitutive nuclear factor kappaB activity and chemoresistance in pancreatic carcinoma cell lines. Cancer Res 62:910–916

    PubMed  CAS  Google Scholar 

  15. Maihöfner C, Charalambous MP, Bhambra U et al (2003) Expression of cyclooxygenase-2 parallels expression of interleukin-1beta, interleukin-6 and NF-kappaB in human colorectal cancer. Carcinogenesis 24:665–671

    Article  PubMed  Google Scholar 

  16. Wolf JS, Chen Z, Dong G et al (2001) IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. Clin Cancer Res 7:1812–1820

    PubMed  CAS  Google Scholar 

  17. Mukhopadhyay P, Ali MA, Nandi A et al (2006) The cyclin-dependent kinase two inhibitor down-regulates nterleukin-1beta-mediated induction of cyclooxygenase-2 expression in human lung carcinoma cells. Cancer Res 66:1758–1766

    Article  PubMed  CAS  Google Scholar 

  18. Ito H, Kaneko K, Makino R, Konishi K, Kurahashi T et al (2007) Interleukin-1beta gene in esophageal, gastric and colorectal carcinomas. Oncol Rep 18:473–481

    PubMed  CAS  Google Scholar 

  19. Deans DA, Wigmore SJ, Gilmour H, Paterson-Brown S, Ross JA et al (2006) Elevated tumour interleukin-1beta is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer. Br J Cancer 95:1568–1575

    Article  PubMed  CAS  Google Scholar 

  20. Wu IC, Lu CY, Kuo FC, Tsai SM, Lee KW et al (2006) Interaction between cigarette, alcohol and betel nut use on esophageal cancer risk in Taiwan. Eur J Clin Invest 36:236–241

    Article  PubMed  CAS  Google Scholar 

  21. Hu CP, Hsieh HG, Chien KY, Wang PY, Wang CI et al (1984) Biologic properties of three newly established human esophageal carcinoma cell lines. J Natl Cancer Inst 72:577–583

    PubMed  CAS  Google Scholar 

  22. Chen MF, Lee KD, Lu MS, Chen CC, Hsieh MJ et al (2009) The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma. J Mol Med 87:307–320

    Article  PubMed  CAS  Google Scholar 

  23. Baeuerle PA, Henkel T (1994) Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12:141–179

    Article  PubMed  CAS  Google Scholar 

  24. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310

    Article  PubMed  CAS  Google Scholar 

  25. Wu CS, Chen MF, Lee IL, Tung SY (2007) Predictive role of nuclear factor-kappaB activity in gastric cancer: a promising adjuvant approach with caffeic acid phenethyl ester. J Clin Gastroenterol 41:894–900

    Article  PubMed  CAS  Google Scholar 

  26. Yamanaka N, Morisaki T, Nakashima H et al (2004) Interleukin 1beta enhances invasive ability of gastric carcinoma through nuclear factor-kappaB activation. Clin Cancer Res 10:1853–1859

    Article  PubMed  CAS  Google Scholar 

  27. Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227

    Article  PubMed  CAS  Google Scholar 

  28. Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS et al (1999) Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res 59:2347–2352

    PubMed  CAS  Google Scholar 

  29. Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB (1996) Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 93:9090–9095

    Article  PubMed  CAS  Google Scholar 

  30. Chiao C, Carothers AM, Grunberger D, Solomon G, Preston GA et al (1995) Apoptosis and altered redox state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast cells. Cancer Res 55:3576–3583

    PubMed  CAS  Google Scholar 

  31. Chen MF, Keng PC, Lin PY, Yang CT, Liao SK et al (2005) Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo. BMC Cancer 5:158

    Article  PubMed  Google Scholar 

  32. Kim MK, Cho KJ, Kwon GY, Park SI, Kim YH et al (2008) ERCC1 predicting chemoradiation resistance and poor outcome in oesophageal cancer. Eur J Cancer 44:54–60

    Article  PubMed  CAS  Google Scholar 

  33. Chen MF, Fang FM, Lu CH, Lu MS, Chen WC et al (2008) Significance of nuclear accumulation of Foxo3a in esophageal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 71:1220–1229

    Article  PubMed  CAS  Google Scholar 

  34. Brown JM, Attardi LD (2005) The role of apoptosis in cancer development and treatment response. Nat Rev Cancer 5:231–237

    Article  PubMed  CAS  Google Scholar 

  35. Olive PL, Banath JP (2004) Phosphorylation of histone H2AX as a measure of radiosensitivity. Int J Radiat Oncol Biol Phys 58:331–335

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The grant was supported by the National Science Council, Taiwan grant 98-2314-B-182-038-MY2.

Competing interests

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, Taiwan

    Miao-Fen Chen & Wen-Cheng Chen

  2. Chang Gung University, College of Medicine, Taoyuan, Taiwan

    Miao-Fen Chen, Wen-Cheng Chen & Kuan-Der Lee

  3. Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, Taiwan

    Ming-Shian Lu

  4. Department of Hematology and Oncology, Chang-Gung Memorial Hospital, Chia-Yi, #6, Chia-Pu Rd, Putz City, Chia-Yi Hsien, Taiwan

    Ping-Tsung Chen & Kuan-Der Lee

  5. Department of Pathology, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, Taiwan

    Paul-Yang Lin

Authors
  1. Miao-Fen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-Shian Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping-Tsung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-Cheng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul-Yang Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kuan-Der Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kuan-Der Lee.

Electronic supplementary materials

Below is the link to the electronic supplementary material.

ESM 1

DOC 271 kb

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, MF., Lu, MS., Chen, PT. et al. Role of interleukin 1 beta in esophageal squamous cell carcinoma. J Mol Med 90, 89–100 (2012). https://doi.org/10.1007/s00109-011-0809-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-011-0809-4

Keywords

Search

Navigation