The macrophage galactose-type C-type lectin 1 receptor plays a major role in mediating colitis-associated colorectal cancer malignancy.

Abstract

Cancer-associated aberrant glycosylation can be detected by the macrophage galactose-type C-type lectin (MGL) receptor; however, whether this interaction enhances or deadens cancer development along with the associated immune response has not been well established. To determine the role of mouse MGL1 in colitis-associated colon cancer (CAC), azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumor development was compared between Mgl1 knockout (Mgl1^-/-) mice and their wild-type (WT) littermates. At 75 days post-CAC induction, colon tumor tissue contained more highly glycosylated proteins, representing potential ligands for the mMGL1 receptor, than did healthy colon tissue. The Mgl1^-/- CAC mice scored lower in disease activity indices and had fewer colonic tumors. In addition, the colonic crypt architecture was less damaged, and mucin production was more significant than in the WT CAC mice. Furthermore, Mgl1^-/- CAC mice displayed higher percentages of CD4⁺ and CD8⁺ T cells in the peripheral blood, and colonic lamina propria; and lower percentages of myeloid-derived suppressor cells (MDSCs). Additionally, less macrophage (Mφ) and natural killer (NK) cell infiltration and lower levels of iNOS and arginase were found in the tumor microenvironment of Mgl1^-/- CAC mice compared with WT mice. These results suggest that the mMGL1 receptor may recognize aberrant glycosylation in colon cancer, which may trigger an inflammatory microenvironment and favor colon tumorigenesis.