Abstract 6139: GPR4 promotes the development of colitis-associated colorectal cancer in an experimental mouse model

Abstract

Abstract GPR4 is a proton-sensing G protein-coupled receptor expressed in endothelial cells as well as other cell types. Endothelial cell adhesion, blood vessel permeability, leukocyte infiltration, and angiogenesis are regulated by the proinflammatory functions of GPR4. Inhibition of GPR4 ameliorates inflammatory bowel disease (IBD) in mouse models. GPR4 expression is upregulated in the intestinal tissues of IBD and colorectal cancer patients and is associated with a worse prognosis. Herein, we studied the role of GPR4 in colitis-associated colorectal cancer (CAC) by inducing CAC in GPR4 knockout (KO) and wild-type (WT) mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). The severity of CAC development was higher in WT mice than GPR4 KO mice when treated with AOM/DSS. Blood vessel density was significantly higher within the tumors of WT mouse colons compared to GPR4 KO mice. GPR4 KO tumors showed a significant increase in tumor necrosis in comparison to WT tumors. Fecal blood/diarrhea score, colon shortening, and mesenteric lymph node size were aggravated in WT mice compared to GPR4 KO mice treated with AOM/DSS. Our data demonstrate that GPR4 increases intestinal inflammation and angiogenesis, enhancing tumor development in the CAC mouse model, suggesting that GPR4 inhibition may reduce the risk of developing colitis-associated colorectal cancer. Citation Format: Mona A. Marie, Edward J. Sanderlin, Alexander Hoffman, Li V. Yang. GPR4 promotes the development of colitis-associated colorectal cancer in an experimental mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6139.