GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models
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)...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/20/4974 |
| _version_ | 1797574321033445376 |
|---|---|
| author | Mona A. Marie Edward J. Sanderlin Alexander P. Hoffman Kylie D. Cashwell Swati Satturwar Heng Hong Ying Sun Li V. Yang |
| author_facet | Mona A. Marie Edward J. Sanderlin Alexander P. Hoffman Kylie D. Cashwell Swati Satturwar Heng Hong Ying Sun Li V. Yang |
| author_sort | Mona A. Marie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T21:22:18Z |
| format | Article |
| id | doaj.art-289a2bc5caf142e29fcd2034e126f4b3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:22:18Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-289a2bc5caf142e29fcd2034e126f4b32023-11-19T15:58:46ZengMDPI AGCancers2072-66942023-10-011520497410.3390/cancers15204974GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine ModelsMona A. Marie0Edward J. Sanderlin1Alexander P. Hoffman2Kylie D. Cashwell3Swati Satturwar4Heng Hong5Ying Sun6Li V. Yang7Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USADepartment of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USAGPR4 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.https://www.mdpi.com/2072-6694/15/20/4974inflammationcancerinflammatory bowel disease (IBD)colitis-associated colorectal cancerGPR4G protein-coupled receptor (GPCR) |
| spellingShingle | Mona A. Marie Edward J. Sanderlin Alexander P. Hoffman Kylie D. Cashwell Swati Satturwar Heng Hong Ying Sun Li V. Yang GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models Cancers inflammation cancer inflammatory bowel disease (IBD) colitis-associated colorectal cancer GPR4 G protein-coupled receptor (GPCR) |
| title | GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models |
| title_full | GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models |
| title_fullStr | GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models |
| title_full_unstemmed | GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models |
| title_short | GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models |
| title_sort | gpr4 knockout attenuates intestinal inflammation and forestalls the development of colitis associated colorectal cancer in murine models |
| topic | inflammation cancer inflammatory bowel disease (IBD) colitis-associated colorectal cancer GPR4 G protein-coupled receptor (GPCR) |
| url | https://www.mdpi.com/2072-6694/15/20/4974 |
| work_keys_str_mv | AT monaamarie gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT edwardjsanderlin gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT alexanderphoffman gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT kyliedcashwell gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT swatisatturwar gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT henghong gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT yingsun gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels AT livyang gpr4knockoutattenuatesintestinalinflammationandforestallsthedevelopmentofcolitisassociatedcolorectalcancerinmurinemodels |