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

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 a...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2015-02, Vol.64 (2), p.181-190
Main Authors: Cui, Guanglin, Qi, Haili, Gundersen, Mona D., Yang, Hang, Christiansen, Ingrid, Sørbye, Sveinung W., Goll, Rasmus, Florholmen, Jon
Format: Article
Language:English
Subjects:
Adenoma - metabolism
Adenoma - mortality
Adenoma - pathology
Adenoma - surgery
Adenoma-carcinoma transition
Adult
Aged
Aged, 80 and over
Basale medisinske, odontologiske og veterinærmedisinske fag: 710
Basic medical, dental and veterinary science disciplines: 710
Biopsy
Cancer Research
Clinical medical disciplines: 750
Colorectal cancer
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Colorectal Neoplasms - surgery
Cytokines
Disease Progression
Gastroenterology
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Immunology
Interleukin-1 Receptor-Like 1 Protein
Interleukin-33
Interleukins - genetics
Interleukins - metabolism
Investigations
Klinisk medisinske fag: 750
Medical disciplines: 700
Medical immunology: 716
Medical prognosis
Medicine
Medicine & Public Health
Medisinsk immunologi: 716
Medisinske Fag: 700
Metastasis
Middle Aged
Neoplasm Grading
Neoplasm Staging
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Oncology
Oncology: 762
Onkologi: 762
Original
Original Article
Pathogenesis
Phenotype
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction
ST2
Stromal Cells - metabolism
Stromal Cells - pathology
Transcription, Genetic
Tumor Microenvironment - genetics
Tumors
VDP
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Description
Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-014-1624-x