Friedman, David

Abstract Description The lifetime risk for colorectal cancer in the United States is approximately 4%. Individuals with Inflammatory Bowel Disease, including Ulcerative Colitis and Crohn’s Disease, have a substantially increased risk of developing colorectal cancer. The mechanisms for accelerated tumorigenesis due to enhanced inflammation are not fully characterized. Siglecs (sialic acid immunoglobulin lectin-like proteins) are a family of inhibitory receptors that are negative regulators of the immune response. Siglec-E is an inhibitory receptor that is expressed by innate immune cells, including monocytes, macrophages, neutrophils, and dendritic cells. Interestingly, mice deficient in Siglec-E have accelerated the development of tumors and reduced survival in a spontaneous mouse model of colorectal cancer (TS4-cre LSL-KRasG12D APClox468/wt). Siglec-E knockout mice also have accelerated gut inflammation using the DSS colitis model as compared to WT mice. Using the DSS/AOM model of colitis-associated colorectal cancer, we found that Siglec-E KO mice develop more tumors as compared to wild-type controls. Thus, Siglec-E is an important regulator of gut homeostasis, and the loss of Siglec-E accelerates colon cancer in two murine models. Funding Sources Mayo Clinic Center for Biomedical Discovery NIH R01 CA243545-01A1 to VSS T32 AI170478 Mayo Clinic Graduate School of Biomedical Sciences Deans fellowship: Initiative for maximizing student development (IMSD) R25 GM055252-26 Doyon Foundation Topic Categories Mucosal and Regional Immunology (MUC)