title: Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner.
abstract: Molecules highly expressed in tumor endothelial cells (TEC) are important for specific targeting of these cells. Previously, using DNA microarray analysis, we found that the prostacyclin receptor (IP receptor) gene was upregulated in TEC compared with normal endothelial cells (NEC). Although prostacyclin is implicated in re-endothelialization and angiogenesis, its role remains largely unknown in TEC. Moreover, the effect of the IP receptor on TEC has not been reported. In the present study we investigated the function of the IP receptor in TEC. The TEC were isolated from two types of human tumor xenografts in nude mice, while NEC were isolated from normal counterparts. Prostacyclin secretion levels in TEC were significantly higher than those in NEC, as shown using ELISA. Real-time RT-PCR showed that the IP receptor was upregulated in TEC compared with NEC. Furthermore, migration and tube formation of TEC were suppressed by the IP receptor antagonist RO1138452. Immunohistostaining showed that the IP receptor was specifically expressed in blood vessels of renal cell carcinoma specimens, but not in glomerular vessels of normal renal tissue. These findings suggest that the IP receptor is a TEC-specific marker and might be a useful therapeutic target.
authors.affiliation: Department of Vascular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osawa
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hida
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kitayama
authors.forename: Kosuke
authors.initials: K
authors.lastname: Akiyama
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Onodera
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujie
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044006:Receptors, Epoprostenol / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: C514222:(2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline); D001593:Benzyl Compounds; D014408:Biomarkers, Tumor; D007093:Imidazoles; D012333:RNA, Messenger; D044006:Receptors, Epoprostenol; D011464:Epoprostenol