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RNA-seq analysis of colon tumors collected from St2-/- and WT reciprocal bone marrow chimeric mice treated with azoxymethane.

ABSTRACT: Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of pre-existing inflammation. We demonstrated that genetic ablation of St2 enhanced colon tumor development. In reciprocal bone marrow (BM) chimeras, the concurrent loss of IL33 signaling within radioresistant nonhematopoietic, and the radiosensitive hematopoietic, compartments was associated with increased tumor burden. To elucidate the molecular mechanisms underpinning the tumor-suppressing effect of IL33 signaling in sporadic colon cancer, we performed whole transcriptome analysis of tumors collected from each of the four cohorts of the 6xAOM-treated BM chimeras. We discovered that St2 deficiency within the nonhematopoietic compartment coincided with suppression of an IFN gene expression signature. The decrease of this IFN gene expression signature was associated with more aggressive disease in human colon cancer patients, suggesting that lack of IL33 signaling impaired the generation of a potent IFN-mediated antitumor immune response. Collectively, our data reveal that IL33 functions as a tumor suppressor in sporadic colon cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE109694 | GEO | 2018/01/27

REPOSITORIES: GEO

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