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

Guanglin, Cui; Qi, Haili; Gundersen, Mona Dixon; Yang, Hang; Christiansen, Ingrid B; Sørbye, Sveinung Wergeland; Goll, Rasmus; Florholmen, Jon
Journal article
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IL33+in_CRC_September_23-2013_MDG_RGO_sws_wotc.pdf (214.3Kb)
URI
http://hdl.handle.net/11250/282340
Date
2014
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  • Artikler, rapporter og annet (FSH) [301]
Original version
Cancer Immunology and Immunotherapy 2014   10.1007/s00262-014-1624-x
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.
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