An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer
O'Donnell, Charlotte; Mahmoud, Amr; Keane, Jonathan; Murphy, Carola T.; White, Declan; Carey, Sinead; O'Riordain, Micheal G.; Bennett, Michael W.; Brint, Elizabeth K.; Houston, Aileen M.
Date:
2015-12-17
Copyright:
© 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/
Citation:
O'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.2015.433
Abstract:
Background: 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.
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