American Association for Cancer Research
Browse

Supplemental Figure 2 from Mast Cell–Derived Prostaglandin D2 Inhibits Colitis and Colitis-Associated Colon Cancer in Mice

Download (3.29 MB)
figure
posted on 2023-03-30, 22:04 authored by Koichi Iwanaga, Tatsuro Nakamura, Shingo Maeda, Kosuke Aritake, Masatoshi Hori, Yoshihiro Urade, Hiroshi Ozaki, Takahisa Murata

Supplemental Figure 2

History

ARTICLE ABSTRACT

Compared with prostaglandin E2, which has an established role in cancer, the role of the COX metabolite prostaglandin D2 (PGD2) in chronic inflammation leading to tumorigenesis is uncertain. In this study, we investigated the role of PGD2 in colitis and colitis-associated colon cancer (CAC) using genetically modified mice and an established model of inflammatory colon carcinogenesis. Systemic genetic deficiency in hematopoietic PGD synthase (H-PGDS) aggravated colitis and accelerated tumor formation in a manner associated with increased TNFα expression. Treatment with a TNFα receptor antagonist attenuated colitis regardless of genotype. Histologic analysis revealed that infiltrated mast cells strongly expressed H-PGDS in inflamed colons. Mast cell–specific H-PGDS deficiency also aggravated colitis and accelerated CAC. In contrast, treatment with a PGD2 receptor agonist inhibited colitis and CAC. Together, our results identified mast cell–derived PGD2 as an inhibitor of colitis and CAC, with implications for its potential use in preventing or treating colon cancer. Cancer Res; 74(11); 3011–9. ©2014 AACR.

Usage metrics

    Cancer Research

    Categories

    Keywords

    CarcinogenesisAnimal models of carcinogenesisTumor initiation and promotionGastrointestinal CancersColorectal cancerImmunologyImmune responses to cancerTumor immunology animal modelsPreclinical ModelsAnimal models of cancerProgression, Invasion & MetastasisInflammation and tumor developmentTumor progressionTumor MicroenvironmentTumor microcirculationTumor-stromal cell interactions

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC