| Title: |
IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization |
| Authors: |
Eissmann, MF; Dijkstra, C; Jarnicki, A; Phesse, T; Brunnberg, J; Poh, AR; Etemadi, N; Tsantikos, E; Thiem, S; Huntington, ND; Hibbs, ML; Boussioutas, A; Grimbaldeston, MA; Buchert, M; O’Donoghue, RJJ; Masson, F; Ernst, M |
| Publisher Information: |
NATURE PUBLISHING GROUP |
| Publication Year: |
2019 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
NHMRC/1069024; https://hdl.handle.net/11343/245968 |
| Availability: |
https://hdl.handle.net/11343/245968 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.FB6E4580 |
| Database: |
BASE |