751c Effectiveness of the Third Eye Retroscope for Detecting Polyps in the Right Colon

Abstract

Background & Aims: Lysophosphatidic acid (LPA), a naturally produced phospholipid, mediates multiple effects that are vital to disease process, including cancer and inflammation. The expression of LPA receptor 2 (LPA2) is up-regulated in several types of cancer, including ovary and colon cancer (CC), but the importance of LPA and LPA2 in the development and progression of CC is unclear. Chronic inflammation is also a risk factor for CC. In this study, we sought to determine whether LPA and LPA2 regulate the progression of CC using animal models of CC. Methods: We examined the potential effects of LPA in CC progression by administering LPA to ApcMin/+ mice. We determined the role of LPA2 in colon tumorigenesis by examining the loss of LPA2 function. We treated LPA2-/mice with azoxymethane (AOM) and dextran sulfate sodium (DSS). Furthermore, we examined the role of LPA2 in modulating intestinal adenoma formation by crossing LPA2-/mice with ApcMin/+ mice. Results: We found that LPA treatment by gavage increased the number of adenomas in small intestine in Apcmin/+ mice. The difference in body weight and mortality suggested that the absence of LPA2 protected animals from the AOM/DSS treatment. LPA2-/mice treated with AOM/DSS showed significantly fewer and smaller tumors in the colon than wild-type (WT) mice. There was no difference in number and size of tumors between LPA2+/and WT mice. We observed reduced epithelial cell proliferation and decreases in β-catenin, Kruppel-like factor 5 (KLF5), and cyclooxygenase-2 (COX-2) expression in LPA2-/mice compared to WT. Compared to WT mice, induction of monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF) was significantly abrogated in LPA2-/mice with reduced infiltration by macrophages. The absence of LPA2 expression in ApcMin/ + mice resulted in a significant decrease in adenomas. At 5 month, ApcMin/+/LPA2-/mice developed an average of 22 adenomas in the small intestine compared with 38 in ApcMin/ +/LPA2+/+ and 43 in ApcMin/+/LPA2+/mice. Consistently, the average number of adenomas in the colon was 2.67, 1.75, and 0.64 for ApcMin/+/LPA2+/+, ApcMin/+/LPA2+/-, and ApcMin/ +/LPA2-/respectively. Adenomas larger than 2 mm accounted for 18% for ApcMin/+/LPA2-/mice in contrast to 38% for ApcMin/+/LPA2+/+. Conclusion: The absence of LPA2 attenuates several effects that may contribute to tumorigenesis In Vivo. Hence, our studies identify LPA2 as a modulator of intestinal tumorigenesis.