title: An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer.
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.
  
  
  CONCLUSIONS
  The IL-33/ST2 signalling axis may have a protective role in colon carcinogenesis.
authors.affiliation: Department of Medicine, University College Cork, Cork, Ireland.
authors.forename: Charlotte
authors.initials: C
authors.lastname: O'Donnell
authors.affiliation: Department of Pathology, University College Cork, Cork, Ireland.
authors.forename: Amr
authors.initials: A
authors.lastname: Mahmoud
authors.affiliation: Department of Medicine, University College Cork, Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Keane
authors.affiliation: Cork Cancer Research Centre, University College Cork, Cork, Ireland.
authors.forename: Carola
authors.initials: C
authors.lastname: Murphy
authors.affiliation: Department of Pathology, University College Cork, Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Declan
authors.initials: D
authors.lastname: White
authors.affiliation: Department of Histopathology, Cork University Hospital, Cork, Ireland.
authors.forename: Sinead
authors.initials: S
authors.lastname: Carey
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Surgery, Mercy University Hospital, Cork, Ireland.
authors.forename: Micheal
authors.initials: M
authors.lastname: O'Riordain
authors.affiliation: Department of Histopathology, Cork University Hospital, Cork, Ireland.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Bennett
authors.affiliation: Department of Pathology, University College Cork, Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Brint
authors.affiliation: Department of Medicine, University College Cork, Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Aileen
authors.initials: A
authors.lastname: Houston
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000032:analysis / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D011956:Receptors, Cell Surface