GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models.

Autor: Marie MA; Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA., Sanderlin EJ; Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA., Hoffman AP; Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA., Cashwell KD; Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA., Satturwar S; Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA., Hong H; Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.; Department of Pathology, Wake Forest University, Winston-Salem, NC 27157, USA., Sun Y; Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA., Yang LV; Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Oct 13; Vol. 15 (20). Date of Electronic Publication: 2023 Oct 13.
DOI: 10.3390/cancers15204974
Abstrakt: 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.
Databáze: MEDLINE
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