Enteric Glia Play a Critical Role in Promoting the Development of Colorectal Cancer.

Autor:	Yuan R; Department of Pathology, Stanford University School of Medicine (Blood Center), Palo Alto, CA, United States., Bhattacharya N; Department of Pathology, Stanford University School of Medicine (Blood Center), Palo Alto, CA, United States., Kenkel JA; Department of Pathology, Stanford University School of Medicine (Blood Center), Palo Alto, CA, United States., Shen J; Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States., DiMaio MA; Department of Pathology, Marin Medical Laboratories, Novato, CA, United States., Bagchi S; Department of Pathology, Stanford University School of Medicine (Blood Center), Palo Alto, CA, United States., Prestwood TR; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, United States., Habtezion A; Division of Gastroenterology and Hepatology, School of Medicine, Stanford University, Stanford, CA, United States., Engleman EG; Department of Pathology, Stanford University School of Medicine (Blood Center), Palo Alto, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2020 Nov 13; Vol. 10, pp. 595892. Date of Electronic Publication: 2020 Nov 13 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.595892
Abstrakt:	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 Apc Min /+ 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. (Copyright © 2020 Yuan, Bhattacharya, Kenkel, Shen, DiMaio, Bagchi, Prestwood, Habtezion and Engleman.)
Databáze:	MEDLINE
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