Marie Mona A, Sanderlin Edward J, Hoffman Alexander P, Cashwell Kylie D, Satturwar Swati, Hong Heng, Sun Ying, Yang Li V
Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Cancers (Basel). 2023 Oct 13;15(20):4974. doi: 10.3390/cancers15204974.
GPR4 is a proton-sensing G protein-coupled receptor highly expressed in vascular endothelial cells and has been shown to potentiate intestinal inflammation in murine colitis models. Herein, we evaluated the proinflammatory role of GPR4 in the development of colitis-associated colorectal cancer (CAC) using the dextran sulfate sodium (DSS) and azoxymethane (AOM) mouse models in wild-type and GPR4 knockout mice. We found that GPR4 contributed to chronic intestinal inflammation and heightened DSS/AOM-induced intestinal tumor burden. Tumor blood vessel density was markedly reduced in mice deficient in GPR4, which correlated with increased tumor necrosis and reduced tumor cell proliferation. These data demonstrate that GPR4 ablation alleviates intestinal inflammation and reduces tumor angiogenesis, development, and progression in the AOM/DSS mouse model.
GPR4是一种质子感应G蛋白偶联受体，在血管内皮细胞中高度表达，并且在小鼠结肠炎模型中已显示出会增强肠道炎症。在此，我们使用葡聚糖硫酸钠（DSS）和氧化偶氮甲烷（AOM）小鼠模型，在野生型和GPR4基因敲除小鼠中评估了GPR4在结肠炎相关结直肠癌（CAC）发生发展中的促炎作用。我们发现GPR4会导致慢性肠道炎症，并增加DSS/AOM诱导的肠道肿瘤负担。GPR4缺陷小鼠的肿瘤血管密度显著降低，这与肿瘤坏死增加和肿瘤细胞增殖减少相关。这些数据表明，在AOM/DSS小鼠模型中，GPR4基因缺失可减轻肠道炎症，并减少肿瘤血管生成、发生和进展。
