AUTHOR=Yuan Robert , Bhattacharya Nupur , Kenkel Justin A. , Shen Jeanne , DiMaio Michael A. , Bagchi Sreya , Prestwood Tyler R. , Habtezion Aida , Engleman Edgar G. 

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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.595892

DOI=10.3389/fonc.2020.595892

ISSN=2234-943X

ABSTRACT=<p>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<sup>+</sup> enteric glia resulted in a profoundly reduced tumor burden in AOM/DSS mice and additionally reduced adenomas in the <italic>Apc<sup>Min</sup></italic><sup>/+</sup> 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<sup>+</sup> enteric glia play a critical pro-tumorigenic role during early CRC development and identify these cells as a potential target for CRC prevention.</p>