RRC ID 30896
Author Iwanaga K, Nakamura T, Maeda S, Aritake K, Hori M, Urade Y, Ozaki H, Murata T.
Title Mast cell-derived prostaglandin D2 inhibits colitis and colitis-associated colon cancer in mice.
Journal Cancer Res
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.
Volume 74(11)
Pages 3011-9
Published 2014-6-1
DOI 10.1158/0008-5472.CAN-13-2792
PII 74/11/3011
PMID 24879565
MeSH Animals Colitis / drug therapy Colitis / genetics Colitis / metabolism* Colitis / pathology Colonic Neoplasms / drug therapy Colonic Neoplasms / genetics Colonic Neoplasms / metabolism* Colonic Neoplasms / pathology Genotype Intramolecular Oxidoreductases / deficiency Intramolecular Oxidoreductases / genetics Intramolecular Oxidoreductases / metabolism Lipocalins / genetics Lipocalins / metabolism Mast Cells / metabolism* Mice Mice, Inbred C57BL Mice, Transgenic Prostaglandin D2 / genetics Prostaglandin D2 / metabolism* Receptors, Immunologic / genetics Receptors, Immunologic / metabolism Receptors, Prostaglandin / genetics Receptors, Prostaglandin / metabolism Signal Transduction Tumor Necrosis Factor-alpha / antagonists & inhibitors Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism
IF 9.727
Times Cited 24
Mice RBRC01888