Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21523
Title: IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization.
Authors: Eissmann, Moritz F;Dijkstra, Christine;Jarnicki, Andrew;Phesse, Toby;Brunnberg, Jamina;Poh, Ashleigh R;Etemadi, Nima;Tsantikos, Evelyn;Thiem, Stefan;Huntington, Nicholas D;Hibbs, Margaret L;Boussioutas, Alex;Grimbaldeston, Michele A;Buchert, Michael;O'Donoghue, Robert J J;Masson, Frederick;Ernst, Matthias
Affiliation: Team 5, Centre of Physiopathology Toulouse-Purpan, INSERM UMR 1043/CNRS UMR 5282, University Toulouse III, CHU Purpan, 31024, Toulouse, France
Cell Signalling and Cell Death Division, Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3052, Australia
Institute of Biochemistry, Goethe University Frankfurt, Frankfurt am Main, 60438, Frankfurt, Germany
Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC, 3010, Australia
Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, 5000, Australia
OMNI-Biomarker Development, Genentech Inc., South San Francisco, CA, 94080, USA
Department of Medicine, University of Melbourne, Melbourne, VIC, 3050, Australia
Department of Immunology and Pathology, Monash University, Melbourne, VIC, 3004, Australia
Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, and Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3052, Australia
Cell Signaling and Cancer Laboratory, European Cancer Stem Cell Research Institute and Cardiff University, Cardiff, CF24 4HQ, UK
Cancer and Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, VIC, 3084, Australia
Issue Date: 21-Jun-2019
EDate: 2019-06-21
Citation: Nature communications 2019; 10(1): 2735
Abstract: The contribution of mast cells in the microenvironment of solid malignancies remains controversial. Here we functionally assess the impact of tumor-adjacent, submucosal mast cell accumulation in murine and human intestinal-type gastric cancer. We find that genetic ablation or therapeutic inactivation of mast cells suppresses accumulation of tumor-associated macrophages, reduces tumor cell proliferation and angiogenesis, and diminishes tumor burden. Mast cells are activated by interleukin (IL)-33, an alarmin produced by the tumor epithelium in response to the inflammatory cytokine IL-11, which is required for the growth of gastric cancers in mice. Accordingly, ablation of the cognate IL-33 receptor St2 limits tumor growth, and reduces mast cell-dependent production and release of the macrophage-attracting factors Csf2, Ccl3, and Il6. Conversely, genetic or therapeutic macrophage depletion reduces tumor burden without affecting mast cell abundance. Therefore, tumor-derived IL-33 sustains a mast cell and macrophage-dependent signaling cascade that is amenable for the treatment of gastric cancer.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21523
DOI: 10.1038/s41467-019-10676-1
ORCID: 0000-0001-9568-4916
0000-0002-7137-1373
0000-0002-6399-1177
PubMed URL: 31227713
Type: Journal Article
Research Support, Non-U.S. Gov't
Appears in Collections:Journal articles

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