Suppression of renal cell carcinoma growth in vivo by forced expression of vascular endothelial growth inhibitor.
Suppression of renal cell carcinoma growth in vivo by forced expression of vascular endothelial growth inhibitor.
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DOI：
10.3892/ijo.2013.1877
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发表时间：
2013-05
影响因子：
5.2
通讯作者：
Ning Zhang;Peng-jie Wu;Duoerkun Shayiremu;Liyang Wu;Hui Shan;L. Ye;Xue-wei Zhao;Jie Cai;W. Jiang;K. Gong;Yong Yang
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文献类型：
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作者：
Ning Zhang;Peng-jie Wu;Duoerkun Shayiremu;Liyang Wu;Hui Shan;L. Ye;Xue-wei Zhao;Jie Cai;W. Jiang;K. Gong;Yong Yang
血管内皮生长抑制因子（VEGI）与某些恶性肿瘤中的肿瘤相关血管有关。然而，其在肾细胞癌（RCC），一种血管生成依赖性肿瘤中的意义仍然未知。在本研究中，我们研究了VEGI在RCC中所起的作用。应用免疫组化和RT-PCR方法检测VEGI在人肾组织和肾癌细胞系中的表达。使用体外和体内模型评价了改变RCC细胞中VEGI表达的生物学影响。我们发现，VEGI mRNA表达在各种各样的人肾细胞癌细胞系，所有的正常肾脏和大多数肾细胞癌组织标本。VEGI蛋白在正常肾小管上皮细胞中表达，但在RCC标本中表达减少或缺失，特别是在高级别肿瘤中。此外，VEGI的强制表达导致抑制血管内皮管的形成，降低RCC细胞在体外的运动和粘附。有趣的是，VEGI的强制表达对RCC细胞的生长、凋亡和侵袭能力没有影响。然而，在异种移植模型中肿瘤生长减少。免疫组织化学染色显示VEGI强制表达的异种移植瘤样品中微血管密度降低。综上所述，我们的研究结果表明，VEGI的表达在肾细胞癌，特别是在较高级别的肿瘤减少。连同其在体内对细胞运动性、粘附、血管内皮管形成和肿瘤生长的抑制作用，这表明VEGI主要通过抑制血管生成起作用，并且在RCC的发展和进展期间是侵袭性的负调节剂。
Vascular endothelial growth inhibitor (VEGI) has been associated with tumor-related vasculature in certain malignancies. However, its implication in renal cell carcinoma (RCC), an angiogenesis-dependent tumor, remains unknown. In the present study, we investigated the role played by VEGI in RCC. The expression of VEGI was examined in human renal tissue and RCC cell lines using immunohistochemical staining and RT-PCR, respectively. The biological impact of modifying the expression of VEGI in RCC cells was evaluated using in vitro and in vivo models. We show that VEGI mRNA is expressed in a wide variety of human RCC cell lines, all of normal renal and most of RCC tissue specimens. VEGI protein expression was observed in normal renal tubular epithelial cells, but was decreased or absent in RCC specimens, particularly in tumors with high grade. Moreover, forced expression of VEGI led to an inhibition of vascular endothelial tube formation, decrease in the motility and adhesion of RCC cells in vitro. Interestingly, forced expression of VEGI had no bearing on growth, apoptosis and invasive capacity of RCC cells. However, tumor growth was reduced in xenograft models. Immunohistochemical staining showed that microvessel density decreased in VEGI forced expression xenograft tumor samples. Taken together, our findings showed that the expression of VEGI is decreased in RCC, particularly in tumors with higher grade. Together with its inhibitory effect on cellular motility, adhesion, vascular endothelial tube formation and tumor growth in vivo, this suggests that VEGI functions mainly through inhibition of angiogenesis and is a negative regulator of aggressiveness during the development and progression of RCC.