title: Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment.
abstract: Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour growth, metastasis and tumour angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes. Circulating and intratumourally administered sST2-Fc fusion protein reduce tumour growth, metastatic spread and tumour angiogenesis in mice bearing high-metastatic CRC. Mechanistically, sST2 suppresses IL-33-induced angiogenesis, Th1- and Th2-responses, macrophage infiltration and macrophage M2a polarization. In conclusion, we show that sST2 negatively regulates tumour growth and the metastatic spread of CRC through modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a potential therapeutic target in CRC.
authors.affiliation: Department of Life Science, Shimane University Faculty of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Akimoto
authors.affiliation: Department of Pathology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Riruke
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Endoscopy Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamaru
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.affiliation: Department of Life Science, Shimane University Faculty of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Takenaga
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000276:immunology*; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33