Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner
Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner
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DOI：
10.1111/j.1349-7006.2012.02261.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.7
通讯作者：
Hida, Kyoko
中科院分区：
文献类型：
--
作者：
Osawa, Takahiro;Ohga, Noritaka;Hida, Kyoko
在肿瘤内皮细胞（TEC）中高度表达的分子对于这些细胞的特异性靶向是重要的。以前，使用DNA微阵列分析，我们发现，前列环素受体（IP受体）基因上调TEC相比，正常内皮细胞（NEC）。虽然前列环素与再内皮化和血管生成有关，但其在TEC中的作用在很大程度上仍然未知。此外，IP受体对TEC的影响尚未报道。在本研究中，我们研究了IP受体在TEC中的功能。TEC从裸鼠中的两种类型的人肿瘤异种移植物中分离，而NEC从正常对应物中分离。前列环素分泌水平TEC显着高于NEC，如使用ELISA所示。Real-time RT-PCR结果显示，TEC中IP受体表达较NEC中上调。IP受体拮抗剂RO 1138452可抑制TEC的迁移和管腔形成。免疫组化结果显示，IP受体在肾癌组织血管中特异性表达，而在正常肾组织的肾小球血管中不表达。这些发现表明IP受体是TEC特异性标志物，可能是有用的治疗靶点。（Cancer Sci 2012; 103：10381044）
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. (Cancer Sci 2012; 103: 10381044)