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

Thumbnail Image
O'Donnell_C_et_al_BJC_2015.pdf(1.39 MB)
Published version
bjc2015433x1.jpg(209.92 KB)
Additional file 1
bjc2015433x2.jpg(483.06 KB)
Additional file 2
bjc2015433x3.jpg(726.46 KB)
Additional file 3
bjc2015433x4.doc(192.5 KB)
Additional file 4
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.
Journal Title
Journal ISSN
Volume Title
Nature Publishing Group
Published Version
Research Projects
Organizational Units
Journal Issue
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
Link to publisher’s version