Peer-Reviewed Journal Details
Mandatory Fields
O'Donnell, C;Mahmoud, A;Keane, J;Murphy, C;White, D;Carey, S;O'Riordain, M;Bennett, MW;Brint, E;Houston, A
2016
January
British Journal of Cancer
An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer
Validated
Optional Fields
CD8(+) T-CELLS HEPATOCELLULAR-CARCINOMA COLORECTAL-CANCER PROGNOSTIC-FACTOR INTERLEUKIN-33 EXPRESSION SERUM METASTASIS EFFECTOR COLITIS
114
37
43
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.
LONDON
0007-0920
10.1038/bjc.2015.433
Grant Details