Activation of mucosal mast cells promotes inflammation-related colon cancer development through recruiting and modulating inflammatory CD11b+Gr1+ cells

Abstract

AbstractMast cells (MCs) have been reported to be one of the important immunoregulatory cells in promoting the development of colitis-related colon cancer (CRC). It is not clear which MC subtypes play critical roles in CRC progression from colitis to cancer because mucosal mast cells (MMCs) are distinct from connective tissue mast cells (CTMCs) in maintaining intestinal barrier function under homeostatic and inflammatory conditions. In the current study, we found that MMC numbers and the gene expressions of MMC-specific proteases increased significantly in an induced CRC murine model. The production of mast cell protease-1 (mMCP-1) after MMC activation not only resulted in the accumulation of CD11b+Gr1+ inflammatory cells in the colon tissues but also modulated the activities of CD11b+Gr1+ cells to support tumor cell growth and to inhibit T cell activation. Blocking the MMC activity in mice that had developed colitis-related epithelium dysplasia, CD11b+Gr1+ infiltration was reduced and CRC development was inhibited. Our results suggest that MMC activation recruited and modulated the CD11b+Gr1+ cells to promote CRC and that MMCs can be potential therapeutic targets for the prevention of CRC development