Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal
Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal
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DOI：
10.1172/jci5028
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发表时间：
1999-01-01
影响因子：
15.9
通讯作者：
Keshet, E
中科院分区：
文献类型：
--
作者：
Benjamin, LE;Golijanin, D;Keshet, E
寻求将肿瘤血管与正常血管区分开的特征以能够破坏预先形成的肿瘤血管。我们发现，在异种移植肿瘤和原发性人类肿瘤的血管中含有相当大比例的尚未招募内皮细胞的未成熟血管。这些未成熟的血管被选择性地闭塞作为血管内皮生长因子（VEGF）撤回的结果。在异种移植的胶质瘤中，未成熟血管对VEGF损失的选择性脆弱性通过使用四环素调节的表达系统下调VEGF转基因表达来证明。在人前列腺癌中，腺上皮的VEGF组成性产生被抑制作为雄激素消融治疗的结果。血管内皮生长因子损失导致，反过来，选择性凋亡的血管内皮细胞没有内皮细胞。这些结果表明，缺乏内皮细胞周围细胞的血管对VEGF的独特依赖性可用于减少现有的肿瘤血管系统。
Features that distinguish tumor vasculatures from normal blood vessels are sought to enable the destruction of preformed tumor vessels. We show that blood vessels in both a xenografted tumor and primary human tumors contain a sizable fraction of immature blood vessels that have not yet recruited periendothelial cells. These immature vessels are selectively obliterated as a consequence of vascular endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the selective vulnerability of immature vessels to VEGF loss was demonstrated by downregulating VEGF transgene expression using a tetracycline-regulated expression system. In human prostate cancer, the constitutive production of VEGF by the glandular epithelium was suppressed as a consequence of androgen-ablation therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in vessels devoid of periendothelial cells. These results suggest that the unique dependence on VEGF of blood vessels lacking periendothelial cells can be exploited to reduce an existing tumor vasculature.