論文 - 詳細
| RRC ID | 3884 |
|---|---|
| 著者 | Murata T, Lin MI, Aritake K, Matsumoto S, Narumiya S, Ozaki H, Urade Y, Hori M, Sessa WC. |
| タイトル | Role of prostaglandin D2 receptor DP as a suppressor of tumor hyperpermeability and angiogenesis in vivo. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Although COX-dependent production of prostaglandins (PGs) is known to be crucial for tumor angiogenesis and growth, the role of PGD(2) remains virtually unknown. Here we show that PGD(2) receptor (DP) deficiency enhances tumor progression accompanied by abnormal vascular expansion. In tumors, angiogenic endothelial cells highly express DP receptor, and its deficiency accelerates vascular leakage and angiogenesis. Administration of a synthetic DP agonist, BW245C, markedly suppresses tumor growth as well as tumor hyperpermeability in WT mice, but not in DP-deficient mice. In a corneal angiogenesis assay and a modified Miles assay, host DP deficiency potentiates angiogenesis and vascular hyperpermeability under COX-2-active situation, whereas exogenous administration of BW245C strongly inhibits both angiogenic properties in WT mice. In an in vitro assay, BW245C does not affect endothelial migration and tube formation, processes that are necessary for angiogenesis; however, it strongly improves endothelial barrier function via an increase in intracellular cAMP production. Our results identify PGD(2)/DP receptor as a new regulator of tumor vascular permeability, indicating DP agonism may be exploited as a potential therapy for the treatment of cancer. |
| 巻・号 | 105(50) |
| ページ | 20009-14 |
| 公開日 | 2008-12-16 |
| DOI | 10.1073/pnas.0805171105 |
| PII | 0805171105 |
| PMID | 19060214 |
| PMC | PMC2596745 |
| MeSH | Animals Capillary Permeability* / drug effects Cell Movement Cell Proliferation Corneal Neovascularization / chemically induced Cyclic AMP / metabolism Endothelium, Vascular / metabolism* Endothelium, Vascular / pathology Hydantoins / pharmacology Interleukin-1beta / pharmacology Mice Mice, Mutant Strains Neoplasms / blood supply* Neovascularization, Pathologic / metabolism* Receptors, Immunologic / agonists Receptors, Immunologic / genetics Receptors, Immunologic / metabolism* Receptors, Prostaglandin / agonists Receptors, Prostaglandin / genetics Receptors, Prostaglandin / metabolism* Vascular Endothelial Growth Factor A / pharmacology |
| IF | 9.412 |
| 引用数 | 58 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC(RCB0558) |