An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer
Murphy, Carola T.
O'Riordain, Micheal G.
Bennett, Michael W.
Brint, Elizabeth K.
Houston, Aileen M.
Nature Publishing Group
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.
Colon cancer , Inflammation , IL-33 ST2 , CD8(+) T-Cells , Hepatocellular-carcinoma , Colorectal cancer , Prognostic factor , Interleukin-33 , Expression , Serum , Metastasis , Effector , Colitis
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