VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5
VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5
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DOI：
10.1016/j.ygyno.2012.05.002
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发表时间：
2012-10-01
影响因子：
4.7
通讯作者：
Wulff, Christine
中科院分区：
文献类型：
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作者：
Herr, Daniel;Sallmann, Alexandra;Wulff, Christine
Objective.目的：探讨卵巢癌患者腹腔组织中VEGF依赖性Claudin 5的表达通过影响内皮细胞的通透性在腹水形成中的作用。本研究采用RT-PCR、VEGF-ELISA和免疫组化双重染色方法检测卵巢癌患者腹水中CD 31和Claudin 5的表达，探讨卵巢癌腹水形成的机制。此外，为了分析VEGF、Claudin 5和内皮通透性的连接，建立了内皮细胞/卵巢癌细胞共培养系统，并通过Western blot分析和通透性测定进行了评估。首先，VEGF基因表达在所有卵巢癌和腹膜活检中得到证实。此外，卵巢癌患者血清和腹水中VEGF的定量显示值显著增加。我们随后证明了在腹膜血管中产生紧密连接蛋白5，其比对照血管中的更弱。对内皮通透性的评估最终显示了通过Claudin 5的VEGF依赖性调节，这提示了卵巢癌患者腹水发生的机制。VEGF诱导卵巢癌患者腹水。这种情况的发生是由于腹膜通透性增加，这是由腹膜内皮中紧密连接蛋白Claudin 5的下调引起的。(C)2012 Elsevier Inc. All rights reserved.
Objective. To evaluate the role of VEGF-dependent Claudin 5 production for the development of ascites via influencing endothelial permeability in peritoneal tissue of ovarian cancer patients.Methods. This study investigates the mechanisms of formation of ascites in ovarian cancer patients, performing RT-PCR, VEGF-ELISA and immunohistochemical dual staining for CD31 and Claudin 5. In addition, in order to analyze the connectivity of VEGF, Claudin 5, and endothelial permeability, an endothelial cell/ovarian cancer cell-co-culture-system was established and evaluated performing Western blot analysis and a permeability assay.Results. Firstly, VEGF-gene expression was demonstrated for all ovarian cancer and peritoneal biopsies. In addition, quantification of VEGF in the serum and ascites of ovarian cancer patients revealed significantly increased values. We subsequently demonstrated Claudin 5 production in the peritoneal vessels, which was weaker than in the vessels of the controls. Evaluation of endothelial permeability finally showed a VEGF-dependent regulation via Claudin 5 suggesting a mechanism for the development of ascites in ovarian cancer patients.Conclusion. VEGF induces ascites in ovarian cancer patients. This instance happens due to increased peritoneal permeability, caused by downregulation of the tight junction protein Claudin 5 in the peritoneal endothelium. (C) 2012 Elsevier Inc. All rights reserved.