Mast cells infiltrating inflamed or transformed gut alternatively sustain mucosal healing or tumor growth

Claudio Tripodo, Carla Guarnotta, Alessia Burocchi, Alice Rigoni, Aroldo Rizzo, Amy Lewis, Luca Danelli, Sabina Sangaletti, Andrew R. Silver, Mario P. Colombo, Lucia Bongiovanni

Risultato della ricerca: Articlepeer review

17 Citazioni (Scopus)

Abstract

Mast cells (MC) are immune cells located next to the intestinal epithelium with regulatory function in maintaining the homeostasis of the mucosal barrier. We have investigated MC activities in colon inflammation and cancer in mice either wildtype (WT) or MC-deficient (KitW-sh) reconstituted or not with bone marrow-derived MCs. Colitis was chemically induced with dextran sodium sulfate (DSS). Tumors were induced by administering azoxymethane (AOM) intraperitoneally before DSS. Following DSS withdrawal, KitW-sh mice showed reduced weight gain and impaired tissue repair compared with their WT littermates or KitW-sh mice reconstituted with bone marrowderived MCs. MCs were localized in areas of mucosal healing rather than damaged areas where they degraded IL33, an alarmin released by epithelial cells during tissue damage. KitW-sh mice reconstituted with MC deficient for mouse mast cell protease 4 did not restore normal mucosal healing or reduce efficiently inflammation after DSS withdrawal. In contrast with MCs recruited during inflammation-associated wound healing, MCs adjacent to transformed epithelial cells acquired a protumorigenic profile. In AOM- and DSS-treated WT mice, high MC density correlated with high-grade carcinomas. In similarly treated KitW-sh mice, tumors were less extended and displayed lower histologic grade. Our results indicate that the interaction of MCs with epithelial cells is dependent on the inflammatory stage, and on the activation of the tissue repair program. Selective targeting of MCs for prevention or treatment of inflammation-associated colon cancer should be timely pondered to allow tissue repair at premalignant stages or to reduce aggressiveness at the tumor stage.
Lingua originaleEnglish
pagine (da-a)3760-3770
Numero di pagine11
RivistaCancer Research
Volume75
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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