IL-1RA suppresses esophageal cancer cell growth by blocking IL-1α

J Clin Lab Anal. 2019 Jul;33(6):e22903. doi: 10.1002/jcla.22903. Epub 2019 May 17.

Abstract

Background: Interleukin-1 promotes tumor angiogenesis through VEGF production. The interleukin-1 receptor antagonist can suppress tumors by blocking this effect.

Methods: Immunohistochemistry, WB, and gene sequencing were used to analyze the expression of IL-1RA in esophageal cancer patients. WB was used to detect the expression of IL-1RA and interleukin-1α in esophageal cancer cells. Stable ESCC cell models overexpressing the IL-1RA were constructed. Their cell functions were tested, and their effects on VEGF were examined.

Results: IL-1RA is downregulated in primary EC tumors, and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. The overexpression of IL-1RA increased the proliferation of KYSE410 EC cells, which have a high level of IL-1α expression. Overexpression of IL-1RA in KYSE410 cells promotes a decrease in the expression of VEGF-A. However, IL-1RA expression did not cause any changes in EC9706 cells with low IL-1α expression.

Conclusion: IL-1RA acts as a tumor suppressor, and its deletion promotes tumor progression by increasing VEGF-A expression in ESCC.

Keywords: IL-1RA; VEGF; esophageal cancer.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics*
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism*
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A