| 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
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Mice |
RBRC01888 |
