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The endogenous anti-angiogenic VEGF isoform, VEGF(165)b inhibits human tumour growth in mice
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 VEGF(xxx), and th...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359649/ https://www.ncbi.nlm.nih.gov/pubmed/18349828 http://dx.doi.org/10.1038/sj.bjc.6604309 |
Sumario: | 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 VEGF(xxx), and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGF(xxx)b, where xxx is the amino acid number. The most studied isoforms, VEGF(165) and VEGF(165)b have been shown to be present in tumour and normal tissues respectively. VEGF(165)b 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 VEGF(165)b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF(165)b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF(165)b can inhibit growth of multiple tumour types in vivo indicating that VEGF(165)b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF(165)b expression by regulation of splicing, overexpression of VEGF(165)b, or therapeutic delivery of VEGF(165)b to tumours. |
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