Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF(121) and VEGF(165) but not VEGF(189)
Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF(121) and VEGF(165) but not VEGF(189)
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DOI：
10.1073/pnas.94.22.12081
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发表时间：
1997-10-28
影响因子：
11.1
通讯作者：
Cavenee, WK
中科院分区：
文献类型：
--
作者：
Cheng, SY;Nagane, M;Cavenee, WK
血管内皮生长因子（vascular endothelial growth factor，VEGF）是一种重要的血管生成调节因子，在正常和病理过程中，包括肿瘤的发生、发展中起重要作用。人U87 MG胶质母细胞瘤细胞表达VEGF的三种亚型：VEGF（121）、VEGF（165）和VEGF（189）。获得过表达每种同种型的克隆并接种到小鼠脑中。接受VEGF（121）-和VEGF（165）-过表达细胞的小鼠在60-90小时后发生脑内出血。相反，植入VEGF（189）-过表达细胞的小鼠仅具有比由亲本细胞引起的肿瘤稍大的肿瘤，并且在植入后的这些早期几乎没有出血的证据，然而，在较长的生长期后，血管生成性和致瘤性明显增强。在肿瘤周围存在由过度表达VEGF（121）和VEGF（165）的细胞引起的快速血管生长和破裂，而在由过度表达VEGF（189）的细胞引起的那些肿瘤附近存在类似的血管形成但没有爆发，并且在由亲本细胞引起的肿瘤边缘上没有爆发。因此，通过将VEGF过表达的胶质母细胞瘤细胞导入脑内，我们建立了一个可重复的和可预测的由单一分子物种的表达增强引起的肿瘤相关脑出血的体内模型，这种模型对于揭示VEGF亚型在血管生成机制中的作用以及研究由于缺血性中风或先天性畸形引起的脑出血是有用的。
The vascular endothelial growth factor (VEGF) has been shown to be a significant mediator of angiogenesis during a variety of normal and pathological processes, including tumor development, Human U87MG glioblastoma cells express the three VEGF isoforms: VEGF(121), VEGF(165), and VEGF(189), Here, we have investigated whether these three isoforms have distinct roles in glioblastoma angiogenesis. Clones that overexpressed each isoform were derived and inoculated into mouse brains, Mice that received VEGF(121)- and VEGF(165)-overexpressing cells developed intracerebral hemorrhages after 60-90 hr, In contrast, mice implanted with VEGF(189)-overexpressing cells had only slightly larger tumors than those caused by parental cells and little evidence of hemorrhage at these early times after implantation, whereas, after longer periods of growth, enhanced angiogenicity and tumorigenicity were apparent, There was rapid blood vessel growth and breakdown around the tumors caused by cells overexpressing VEGF(121) and VEGF(165), whereas there was similar vascularization but no eruption in the vicinity of those tumors caused by cells overexpressing VEGF(189), and none on the border of the tumors caused by the parental cells, Thus, by introducing VEGF-overexpressing glioblastoma cells into the brain, we have established a reproducible and predictable in vivo model of tumor-associated intracerebral hemorrhage caused by the enhanced expression of single molecular species, Such a model should be useful for uncovering the role of VEGF isoforms in the mechanisms of angiogenesis and for investigating intracerebral hemorrhage due to ischemic stroke or congenital malformations.