RRC ID |
43704
|
著者 |
Osawa T, Ohga N, Hida Y, Kitayama K, Akiyama K, Onodera Y, Fujie M, Shinohara N, Shindoh M, Nonomura K, Hida K.
|
タイトル |
Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner.
|
ジャーナル |
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.
|
巻・号 |
103(6)
|
ページ |
1038-44
|
公開日 |
2012-6-1
|
DOI |
10.1111/j.1349-7006.2012.02261.x
|
PMID |
22380928
|
PMC |
PMC7685074
|
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 |
4.966
|
引用数 |
20
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
OS-RC-2(RCB0735) |