The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.
The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.
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DOI：
10.1038/sj.bjc.6604309
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发表时间：
2008-04-08
影响因子：
8.8
通讯作者：
Harper S
中科院分区：
文献类型：
--
作者：
Rennel E;Waine E;Guan H;Schüler Y;Leenders W;Woolard J;Sugiono M;Gillatt D;Kleinerman E;Bates D;Harper S
血管内皮生长因子-A被广泛认为是肿瘤生长所需的血管生成的主要刺激因子。VEGF作为两个家族的多种同种型产生，通过末端外显子中的近端剪接位点选择产生的促血管生成家族，称为VEGFxxx，和通过末端外显子中的远端剪接位点选择形成的抗血管生成家族，称为VEGFxxxb，其中xxx是氨基酸编号。研究最多的同种型VEGF 165和VEGF 165 b已显示分别存在于肿瘤和正常组织中。VEGF 165 b在体外已显示出抑制VEGF和缺氧诱导的血管生成，以及VEGF诱导的细胞迁移和增殖。在这里，我们表明，肿瘤细胞过度表达VEGF 165 b抑制前列腺癌，尤文氏肉瘤和肾细胞癌在异种移植小鼠肿瘤模型的生长。此外，VEGF 165 b过表达抑制肿瘤细胞介导的内皮细胞迁移和增殖。这些数据表明，VEGF 165 b的过表达可以抑制多种肿瘤类型的体内生长，表明VEGF 165 b在许多不同的肿瘤类型中具有作为抗血管生成、抗肿瘤策略的潜力，通过调节剪接、VEGF 165 b的过表达或VEGF 165 b向肿瘤的治疗性递送来控制VEGF 165 b的表达。
Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours.
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影响因子：
8
作者：
Kuesters, B.;Kats, G.;Leenders, W. P. J.
通讯作者：
Leenders, W. P. J.
影响因子：
8.8
作者：
Pritchard-Jones, R. O.;Dunn, D. B. A.;Qiu, Y.;Varey, A. H. R.;Orlando, A.;Rigby, H.;Harper, S. J.;Bates, D. O.
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158.5
作者：
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通讯作者：
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64.8
作者：
SHWEIKI, D;ITIN, A;KESHET, E
通讯作者：
KESHET, E
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8
作者：
Suarez, S. Cebe;Pieren, M.;Ballmer-Hofer, K.
通讯作者：
Ballmer-Hofer, K.