An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer

dc.contributor.authorO'Donnell, Charlotte
dc.contributor.authorMahmoud, Amr
dc.contributor.authorKeane, Jonathan
dc.contributor.authorMurphy, Carola T.
dc.contributor.authorWhite, Declan
dc.contributor.authorCarey, Sinead
dc.contributor.authorO'Riordain, Micheal G.
dc.contributor.authorBennett, Michael W.
dc.contributor.authorBrint, Elizabeth K.
dc.contributor.authorHouston, Aileen M.
dc.contributor.funderHealth Research Boarden
dc.contributor.funderPathological Society of Great Britain and Irelanden
dc.date.accessioned2019-09-05T08:49:56Z
dc.date.available2019-09-05T08:49:56Z
dc.date.issued2015-12-17
dc.date.updated2019-09-02T06:06:15Z
dc.description.abstractBackground: Despite the importance of inflammation in cancer, the role of the cytokine IL-33, and its receptor ST2, in colon cancer is unclear. The aim of this study was to investigate the role of IL-33, and its receptor isoforms (ST2 and ST2L), in colon cancer. Methods: Serum levels of IL-33 and sST2 were determined with ELISA. ST2 and IL-33 expression was detected with quantitative real-time PCR (qRT–PCR), western blotting and immunohistochemistry. ST2 expression in CT26 cells was stably suppressed using ST2-specific shRNA. Cytokine and chemokine gene expression was detected with qRT–PCR. Results: Human colon tumours showed lower expression of ST2L as compared with adjacent non-tumour tissue (P<0.01). Moreover, the higher the tumour grade, the lower the expression of ST2L (P=0.026). Colon cancer cells expressed ST2 and IL-33 in vitro. Functional analyses showed that stimulation of tumour cells with IL-33 induced the expression of chemokine (C–C motif) ligand 2 (CCL2). Knockdown of ST2 in murine colon cancer cells resulted in enhanced tumour growth (P<0.05) in BALB/c mice in vivo. This was associated with a decrease in macrophage infiltration, with IL-33-induced macrophage recruitment reduced by antagonising CCL2 in vitro. Conclusion: The IL-33/ST2 signalling axis may have a protective role in colon carcinogenesis.en
dc.description.sponsorshipHealth Research Board of Ireland (PhD/2007/4); Pathological Society of Great Britain and Ireland (SGS 2014/10/04)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO'Donnell, C., Mahmoud, A., Keane, J., Murphy, C., White, D., Carey, S., O'Riordain, M., Bennett, M. W., Brint, E. and Houston, A. (2015) 'An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer', British Journal Of Cancer, 114, pp. 37-43. doi: 10.1038/bjc.2015.433en
dc.identifier.doi10.1038/bjc.2015.433en
dc.identifier.endpage43en
dc.identifier.issn0007-0920
dc.identifier.journaltitleBritish Journal of Canceren
dc.identifier.startpage37en
dc.identifier.urihttps://hdl.handle.net/10468/8457
dc.identifier.volume114en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttps://www.nature.com/articles/bjc2015433
dc.rights© 2016 Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en
dc.subjectColon canceren
dc.subjectInflammationen
dc.subjectIL-33 ST2en
dc.subjectCD8(+) T-Cellsen
dc.subjectHepatocellular-carcinomaen
dc.subjectColorectal canceren
dc.subjectPrognostic factoren
dc.subjectInterleukin-33en
dc.subjectExpressionen
dc.subjectSerumen
dc.subjectMetastasisen
dc.subjectEffectoren
dc.subjectColitisen
dc.titleAn antitumorigenic role for the IL-33 receptor, ST2L, in colon canceren
dc.typeArticle (peer-reviewed)en
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