VEGF and SEMA4D have synergistic effects on the promotion of angiogenesis in epithelial ovarian cancer.
VEGF and SEMA4D have synergistic effects on the promotion of angiogenesis in epithelial ovarian cancer.
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DOI：
10.1186/s11658-017-0058-9
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发表时间：
2018
影响因子：
8.3
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Chen Y;Zhang L;Liu WX;Wang K
以VEGF为靶点的抗血管生成治疗是晚期卵巢癌的重要治疗策略之一。然而，取决于药剂，治疗可能具有不期望的副作用。SEMA 4D最近因其在促进血管生成中的作用而受到关注。在这里，我们试图进一步了解SEMA 4D促进卵巢癌血管生成的机制。采用相关分析和western blot法检测VEGF与SEMA 4D在临床组织和细胞中的表达关系。采用血管生成拟态和transwell迁移分析检测VEGF、SEMA 4D和plexin-B1在血管生成拟态和迁移中的作用。使用免疫荧光染色法测定EOC临床组织中的血管密度和SEMA 4D表达。Western blot检测CD 31、MMP 2和VE-钙粘蛋白的表达。并分析VEGF-SEMA 4D与恶性肿瘤预后的关系。我们发现VEGF基因敲低可以抑制SEMA 4D的表达，并且VEGF和SEMA 4D在EOC癌组织中的表达呈正相关。血管生成拟态和transwell迁移分析表明，SEMA 4D和VEGF在促进A2780和HUVEC细胞中的血管生成方面具有协同作用。可溶性SEMA 4D（sSEMA 4D）可通过SEMA 4D/plexin-B1通路促进A2780和HUVEC的VM和迁移，而稳定转染shR-plexin-B1的细胞则无此作用。临床上皮性卵巢癌组织中血管密度和SEMA 4D/plexin-B1表达均较高。当VEGF、SEMA 4D和丛蛋白-B1被敲低时，作为血管生成和上皮-间质转化（EMT）过程的标志物和起始物的CD 31、MMP 2和VE-钙粘蛋白的表达减少。VEGF、SEMA 4D与卵巢癌恶性程度呈正相关，SEMA 4D可作为独立的预后因素。VEGF和SEMA 4D在促进上皮性卵巢癌血管生成方面具有协同作用。靶向VEGF和SEMA 4D信号通路可能对EOC的治疗具有重要意义。
Anti-angiogenesis therapy that targets VEGF is one of the important treatment strategies in advanced ovarian cancer. However, depending on the pharmaceutical agent, treatment can have undesirable side effects. SEMA4D has recently gained interest for its role in promoting angiogenesis. Here, we try to further understand the mechanism by which SEMA4D promotes angiogenesis in ovarian cancer. Correlation and western blot assaya were used to detect the relationship between VEGF and SEMA4D in clinical tissues and cells. Vasculogenic mimicry and transwell migration analyses were used to detect the roles of VEGF, SEMA4D and plexin-B1 on vasculogenic mimicry and migration. Vascular density and SEMA4D expression was determined using immunofluorescence staining in clinical tissues of EOC. Western blot was used to detect the expressions of CD31, MMP2 and VE-cadherin. We also analyzed the relationship between VEGF-SEMA4D and malignant tumor prognosis. We found that knockdown of VEGF could suppress SEMA4D expression and that the expressions of VEGF and SEMA4D have a positive correlation in EOC cancer tissues. Vasculogenic mimicry and transwell migration analyses showed that SEMA4D and VEGF have a synergistic effect on the promotion of angiogenesis in A2780 and HUVEC cells. Soluble SEMA4D (sSEMA4D) could promote VM and migration in A2780 and HUVEC cells via the SEMA4D/plexin-B1 pathway, but the effect was not noted in stably transfected shR-plexin-B1 cells. In clinical tissues of EOC, the vascular density and SEMA4D/plexin-B1 expression were higher. When VEGF, SEMA4D and plexin-B1 was knocked down, the expression of CD31, MMP2 and VE-cadherin, which are the markers and initiators of angiogenesis and the epithelial–mesenchymal transition (EMT) process were reduced. VEGF and SEMA4D had a positive correlation with the malignant degree of ovarian cancer, and SEMA4D can serve as an independent prognostic factor. VEGF and SEMA4D have synergistic effects on the promotion of angiogenesis in epithelial ovarian cancer. Targeting VEGF and the SEMA4D signaling pathway could be important for the therapy for EOC.
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影响因子：
64.5
作者：
Fischer, Christian;Jonckx, Bart;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
影响因子：
11.2
作者：
Sitohy B;Nagy JA;Dvorak HF
通讯作者：
Dvorak HF
影响因子：
3.9
作者：
Gianni-Barrera, Roberto;Trani, Marianna;Banfi, Andrea
通讯作者：
Banfi, Andrea
DOI：
10.1073/pnas.0508825103
发表时间：
2006-06-13
影响因子：
11.1
作者：
Basile, John R.;Castilho, Rogerio M.;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio
影响因子：
50.3
作者：
Kong-Beltran, M;Stamos, J;Wickramasinghe, D
通讯作者：
Wickramasinghe, D