The Controversial Role of Intestinal Mast Cells in Colon Cancer

Abstract

Mast cells are tissue-resident sentinels involved in large number of physiological and pathological processes, such as infection and allergic response, thanks to the expression of a wide array of receptors. Mast cells are also frequently observed in a tumor microenvironment, suggesting their contribution in the transition from chronic inflammation to cancer. In particular, the link between inflammation and colorectal cancer development is becoming increasingly clear. It has long been recognized that patients with inflammatory bowel disease have an increased risk of developing colon cancer. Evidence from experimental animals also implicates the innate immune system in the development of sporadically occurring intestinal adenomas, the precursors to colorectal cancer. However, the exact role of mast cells in tumor initiation and growth remains controversial: mast cell-derived mediators can either exert pro-tumorigenic functions, causing the progression and spread of the tumor, or anti-tumorigenic functions, limiting the tumor's growth. Here, we review the multifaceted and often contrasting findings regarding the role of the intestinal mast cells in colon cancer progression focusing on the molecular pathways mainly involved in the regulation of mast cell plasticity/functions during tumor progression.

Keywords: colorectal cancer; mast cells; tumor microenvironment.

Figure 1

Mast cell subsets in murine and human gut. Mast cell subsets identified in murine intestine (left) and human intestine (right), and their distribution are represented with different colors. Proteases expressed by the different MC subsets are listed in the table below. ieMMC: intraepithelial mucosal mast cells, MMC: mucosal mast cells, CTMC: connective tissue mast cells, MC_T, MC_TC, MC_C: Mast cells expressing tryptase, tryptase and chymase, chymase only, respectively.

Figure 2

The dichotomous role of MCs during CRC. MCs infiltrating colonic tumor can directly interact with cancer cells or recognize tumor-released factors, such TSLP, IL-33 and SCF, tuning their phenotype/activity. Different MC subsets can exert either pro-tumorigenic (red arrow) or anti-tumorigenic (blue arrow) properties through the secretion of preformed and newly synthesized mediators, the main of which are depicted. TSLP: thymic stromal lymphopoietin; IL-33: Interleukin-33, SCF: stem cell factor, VEGF: vascular endothelial growth factor; FGF: fibroblast growth factor, TGF: transforming growth factor, ROS: reactive oxygen species, TNF: tumor necrosis factor.