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Role of interleukin 1 beta in esophageal squamous cell carcinoma

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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.

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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

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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.

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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

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  1. Miao-Fen Chen
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Correspondence to Kuan-Der Lee.

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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

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

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