title: Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer.
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.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, 2 Jingba Road, Zhengzhou, 455000, Henan, China, guanglin.cui@hint.no.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Cui
authors.forename: Haili
authors.initials: H
authors.lastname: Qi
authors.forename: Mona D
authors.initials: MD
authors.lastname: Gundersen
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.forename: Ingrid
authors.initials: I
authors.lastname: Christiansen
authors.forename: Sveinung W
authors.initials: SW
authors.lastname: Sørbye
authors.forename: Rasmus
authors.initials: R
authors.lastname: Goll
authors.forename: Jon
authors.initials: J
authors.lastname: Florholmen
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface