Enteric Glia Play a Critical Role in Promoting the Development of Colorectal Cancer
Autor: | Edgar G. Engleman, Sreya Bagchi, Robert Yuan, Jeanne Shen, Tyler R. Prestwood, Michael A. DiMaio, Justin A. Kenkel, Nupur Bhattacharya, Aida Habtezion |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer Population Tumor burden colorectal cancer azoxymethane/dextran sodium sulfate Biology lcsh:RC254-282 Familial adenomatous polyposis 03 medical and health sciences chemistry.chemical_compound enteric nervous system 0302 clinical medicine Immunity ApcMin/+ medicine education Original Research education.field_of_study Azoxymethane lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology Intestinal homeostasis nervous system Oncology chemistry 030220 oncology & carcinogenesis Cancer research enteric glia Enteric nervous system |
Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 10 (2020) |
ISSN: | 2234-943X |
Popis: | Enteric glia are a distinct population of peripheral glial cells in the enteric nervous system that regulate intestinal homeostasis, epithelial barrier integrity, and gut defense. Given these unique attributes, we investigated the impact of enteric glia depletion on tumor development in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice, a classical model of colorectal cancer (CRC). Depleting GFAP+ enteric glia resulted in a profoundly reduced tumor burden in AOM/DSS mice and additionally reduced adenomas in the ApcMin/+ mouse model of familial adenomatous polyposis, suggesting a tumor-promoting role for these cells at an early premalignant stage. This was confirmed in further studies of AOM/DSS mice, as enteric glia depletion did not affect the properties of established malignant tumors but did result in a marked reduction in the development of precancerous dysplastic lesions. Surprisingly, the protective effect of enteric glia depletion was not dependent on modulation of anti-tumor immunity or intestinal inflammation. These findings reveal that GFAP+ enteric glia play a critical pro-tumorigenic role during early CRC development and identify these cells as a potential target for CRC prevention. |
Databáze: | OpenAIRE |
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