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
リソース情報
ヒト・動物細胞