RRC ID 43704
Author Osawa T, Ohga N, Hida Y, Kitayama K, Akiyama K, Onodera Y, Fujie M, Shinohara N, Shindoh M, Nonomura K, Hida K.
Title Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner.
Journal Cancer Sci.
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.
Volume 103(6)
Pages 1038-44
Published 2012-6
DOI 10.1111/j.1349-7006.2012.02261.x
PMID 22380928
MeSH Animals Benzyl Compounds / pharmacology Biomarkers, Tumor Carcinoma, Renal Cell / metabolism* Carcinoma, Renal Cell / pathology* Cell Line, Tumor Cell Movement Endothelial Cells / metabolism Endothelial Cells / pathology* Endothelium, Vascular / pathology Endothelium, Vascular / physiology Epoprostenol / biosynthesis Humans Imidazoles / pharmacology Mice Mice, Nude Neoplasm Transplantation Neovascularization, Pathologic* RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Epoprostenol / antagonists & inhibitors Receptors, Epoprostenol / biosynthesis Receptors, Epoprostenol / metabolism* Transplantation, Heterologous
IF 4.372
Times Cited 14
Human and Animal Cells