Open Access<p>Aryl hydrocarbon receptor acts as a tumor suppressor in a syngeneic MC38 colon carcinoma tumor model</p>
Author(s) -
Poonam Yakkundi,
Eleanor Gonsalves,
Maria Galou-Lameyer,
Mark Selby,
William K. Chan
Publication year - 2019
Publication title -
hypoxia
Language(s) - English
Resource type - Journals
ISSN - 2324-1128
DOI - 10.2147/hp.s196301
Subject(s) - aryl hydrocarbon receptor , tumor microenvironment , cancer research , tumor progression , immune system , cytotoxic t cell , flow cytometry , tumor necrosis factor alpha , chemistry , biology , immunology , medicine , cancer , in vitro , transcription factor , biochemistry , gene
Background: Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. It has been reported that AHR can act as a tumor promoter or a tumor suppressor, depending on the tumor type. Methods: In an effort to understand the role played by AHR in tumor growth, the MC38 syngeneic colon carcinoma tumor model was used on C57BL/6 or ahr knockout (KO, -/-) mice with or without AHR antagonist (CH223191) treatment. Tumor sizes were measured, and biomarkers were quantified in tumor microenvironment and draining lymph nodes using flow cytometry. Enzyme-linked immunosorbent assay was used to determine the amount of cytokines in tumors. Results: In ahr deficient mice, MC38 tumors progress more rapidly than in wild-type mice, accompanied by an increase in tumor-associated macrophages and M2 macrophages and a decrease in CD8a positive cytotoxic lymphocytes. Analysis of cytokines in the tumor microenvironment reveals a pro-inflammatory phenotype. Similar changes were observed by pharmacologic blockade of the receptor using CH223191. Conclusion: AHR acts as a tumor suppressor in mice implanted with MC38 colon carcinoma cells as evidenced by either a blockade or deficiency of AHR.