ArticleProceedings of the National Academy of Sciences of the United States of America2015
IL-33 activates tumor stroma to promote intestinal polyposis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Pooled it
- Critical role of interleukin-33 in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- The IL-33-ILC2 axis: a key regulator of type 2 immunity in respiratory disease.Frontiers in immunology · 2026Review
- Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis.Mucosal immunology · 2025Article
- The role of IL-33/ST2 axis in esophageal inflammatory diseases and cancers: implications for the immunopathogenesis and immunotherapeutic target?Therapeutic advances in gastroenterology · 2025Review
- Tumor-infiltrating mast cells stimulate ICOSJournal of advanced research · 2024Article
- The Importance of Th2 Immune Responses in Mediating the Progression of Gastritis-Associated Metaplasia to Gastric Cancer.Cancers · 2024Review
- Unveiling the immune symphony: decoding colorectal cancer metastasis through immune interactions.Frontiers in immunology · 2024Review
- Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.International journal of biological sciences · 2024Review
- Article
- Regulatory T cells in the face of the intestinal microbiota.Nature reviews. Immunology · 2023Review
- SCF and IL-33 regulate mouse mast cell phenotypic and functional plasticity supporting a pro-inflammatory microenvironment.Cell death & disease · 2023Article
- A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut.International journal of molecular sciences · 2023Review
- Discovery of highly immunogenic spleen-resident FCGR3Cellular & molecular immunology · 2023Article
- Review
- RBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways.JCI insight · 2023Article
- Hypoxia induces downregulation of the tumor-suppressive sST2 in colorectal cancer cells via the HIF-nuclear IL-33-GATA3 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring.Journal of clinical medicine · 2023Review
- Review
- Knowledge mapping and research trends of IL-33 from 2004 to 2022: a bibliometric analysis.Frontiers in immunology · 2023Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc(Min/+) mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc(Min/+) polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc(Min/+) polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.