SCF and IL-33 regulate mouse mast cell phenotypic and functional plasticity supporting a pro-inflammatory microenvironment

Author:

Molfetta RosaORCID,Lecce Mario,Milito Nadia D.,Putro ErisaORCID,Pietropaolo Giuseppe,Marangio Caterina,Scarno GianlucaORCID,Moretti MartaORCID,De Smaele EnricoORCID,Santini Tiziana,Bernardini Giovanni,Sciumè Giuseppe,Santoni Angela,Paolini RossellaORCID

Abstract

AbstractMast 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)-α. 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-α maintains a pro-inflammatory microenvironment.

Funder

Associazione Italiana per la Ricerca sul Cancro

Istituto Pasteur-Fondazione Cenci Bolognetti

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

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