Molfetta, Rosa and Lecce, Mario and Milito, Nadia D. and Putro, Erisa and Pietropaolo, Giuseppe and Marangio, Caterina and Scarno, Gianluca and Moretti, Marta and De Smaele, Enrico and Santini, Tiziana and Bernardini, Giovanni and Sciume, Giuseppe and Santoni, Angela and Paolini, Rossella (2023) SCF and IL-33 regulate mouse mast cell phenotypic and functional plasticity supporting a pro-inflammatory microenvironment. CELL DEATH & DISEASE, 14 (9): 616. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). Several recent findings support their contribution to the transition from chronic inflammation to cancer. However, MC-derived mediators can either favor tumor progression, inducing the spread of the tumor, or exert anti-tumorigenic functions, limiting tumor growth. This apparent controversial role likely depends on the plastic nature of MCs that under different microenvironmental stimuli can rapidly change their phenotype and functions. Thus, the exact effect of unique MC subset(s) during tumor progression is far from being understood. Using a murine model of colitis-associated colorectal cancer, we initially characterized the MC population within the TME and in non-lesional colonic areas, by multicolor flow cytometry and confocal microscopy. Our results demonstrated that tumor-associated MCs harbor a main connective tissue phenotype and release high amounts of Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-alpha. This MC phenotype correlates with the presence of high levels of Stem Cell Factor (SCF) and IL-33 inside the tumor. Thus, we investigated the effect of SCF and IL-33 on primary MC cultures and underscored their ability to shape MC phenotype eliciting the production of pro-inflammatory cytokines. Our findings support the conclusion that during colonic transformation a sustained stimulation by SCF and IL-33 promotes the accumulation of a prevalent connective tissue-like MC subset that through the secretion of IL-6 and TNF-alpha maintains a pro-inflammatory microenvironment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-KIT; TRICHINELLA-SPIRALIS; INNATE IMMUNITY; INTERLEUKIN-33; MICE; ACTIVATION; EXPRESSION; CYTOKINE; SURVIVAL; PROMOTE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Apr 2024 12:51 |
| Last Modified: | 18 Apr 2024 12:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60822 |
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