Journal article
IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization
MF Eissmann, C Dijkstra, A Jarnicki, T Phesse, J Brunnberg, AR Poh, N Etemadi, E Tsantikos, S Thiem, ND Huntington, ML Hibbs, A Boussioutas, MA Grimbaldeston, M Buchert, RJJ O’Donoghue, F Masson, M Ernst
Nature Communications | Published : 2019
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 re..
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Awarded by Ludwig Institute for Cancer Research
Funding Acknowledgements
We thank the animal facility staff of La Trobe University and the Ludwig Institute for Cancer Research as well as the Austin and WEHI histology department for technical assistance. We also acknowledge the excellent support for cell sorting by David Baloyan (ONJCRI) and image generation and analysis by Cameron Nowell (Monash University) and Lachlan Whitehead (WEHI). This work was supported through the Victorian State Government Operational Infrastructure Support, the Nation Health and Medical Research Council (NHMRC) of Australia grants 1092788, 1067244, 1069024 and Cancer Council Victoria's Grant-in-Aid 1160708. M.E. is a NHMRC Principal Research Fellow and also received funding from Ludwig Cancer Research.