Abstract 634: Hypercholesterolemia Increases the Incidence of Colorectal Neoplasia by Impairing Hematopoietic Stem Cell Differentiation Towards Nkt and γδ T Cells

Rationale: Hypercholesterolemia, a co-morbidity of obesity, is one of the most common diet-related metabolic disorders and is an independent risk factor for colorectal neoplasia. As yet, no generalizable mechanism has been described to show how hypercholesterolemia increases the risk of cancer especially that of colorectal neoplasia. Objective: We hypothesized that hypercholesterolemia impaired the differentiation of hematopoietic stem cells (HSCs) toward the cellular components critical to immunosurveillance against colorectal neoplasia. Identifying the mechanisms by which hypercholesterolemia affects HSC differentiation may provide clues to understanding how hypercholesterolemia increases all-cause mortality and especially that of colorectal cancer in divergent clinical studies. Methods and Results: Two different hypercholesterolemic mice were applied in the study, including ApoE-/- mouse and high cholesterol diet fed WT mouse. Colorectal neoplasia was induced by IP injection of AOM. The incidence of co...