Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

Cancer Immunol Immunother. 2015 Feb;64(2):181-90. doi: 10.1007/s00262-014-1624-x. Epub 2014 Oct 17.

Abstract

Most sporadic colorectal cancers (CRCs) develop from preformed adenomas. Cytokines are involved in the transition from adenoma to CRC. Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family and involved in the development of chronic inflammation and cancer. The aim of this study was to evaluate the dynamics of the IL-33/ST2 axis during the sequence of progression from normal colorectum to adenoma to carcinoma and to investigate the association of IL-33 and ST2 expression with clinicopathological parameters and prognosis. The results demonstrated that the levels of IL-33 and ST2 in adenomas (n = 50), determined by real-time PCR, were significantly higher than those of normal controls (n = 30); the levels of both IL-33/ST mRNA in CRCs (n = 50) were higher than in normal controls but lower than in adenomas. Further analysis revealed that the expression level of ST2 in CRCs was associated with tumor/node/metastasis (TNM) stage. The log-rank test showed that neither the IL-33 nor the ST2 expression level was correlated with overall survival in patients with CRC. The increased expression of IL-33/ST2 in adenomas and CRC tissues was confirmed by immunohistochemistry and was observed in both the tumor stromal cells and adenomatous/cancerous cells. Notably, increased densities of IL-33-positive and ST2-positive microvessels were found in the stroma of adenomas and CRCs. In conclusion, increased expression of the IL-33/ST2 axis along the colorectal adenoma-carcinoma sequence might be involved in the neoplastic transformation via the participation of this axis in the regulation of angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / mortality
  • Adenoma / pathology*
  • Adenoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transcription, Genetic
  • Tumor Microenvironment / genetics

Substances

  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • RNA, Messenger
  • Receptors, Cell Surface