Nieto-Yañez Oscar, Navia Sonia H, Juárez-Avelar Imelda, Rodríguez Tonathiu, Andrade-Meza Antonio, Ortiz-Sánchez Betsaida J, Mendoza-Rodríguez Mónica G, Olguín Jonadab E, Reyes José L, Montes de Oca-Samperio Daniel, Salinas Lara Citlaltepetl, Terrazas Luis I, Rodriguez-Sosa Miriam
Innate Immunity Laboratory, Biomedicine Research Unit (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, State of Mexico, Mexico.
Doctoral Program in Biological Sciences, UNAM, Mexico City, Mexico.
Immunol Cell Biol. 2025 May;103(5):444-460. doi: 10.1111/imcb.70011. Epub 2025 Mar 3.
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.
癌症相关的异常糖基化可通过巨噬细胞半乳糖型C型凝集素（MGL）受体检测到；然而，这种相互作用是增强还是抑制癌症发展以及相关的免疫反应，尚未得到充分证实。为了确定小鼠MGL1在结肠炎相关结肠癌（CAC）中的作用，比较了Mgl1基因敲除（Mgl1 -/-）小鼠与其野生型（WT）同窝小鼠在氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导下的肿瘤发展情况。在CAC诱导后75天，结肠肿瘤组织中含有比健康结肠组织更多的高度糖基化蛋白，这些蛋白代表了mMGL1受体的潜在配体。Mgl1 -/- CAC小鼠的疾病活动指数得分较低，结肠肿瘤较少。此外，与WT CAC小鼠相比，Mgl1 -/- CAC小鼠的结肠隐窝结构受损较轻，粘蛋白产生更为显著。此外，Mgl1 -/- CAC小鼠外周血和结肠固有层中CD4和CD8 T细胞的百分比更高；骨髓来源的抑制细胞（MDSC）的百分比更低。此外，与WT小鼠相比，在Mgl1 -/- CAC小鼠的肿瘤微环境中发现巨噬细胞（Mφ）和自然杀伤（NK）细胞浸润较少，iNOS和精氨酸酶水平较低。这些结果表明，mMGL1受体可能识别结肠癌中的异常糖基化，这可能引发炎症微环境并促进结肠肿瘤发生。
