VASCULAR ENDOTHELIAL GROWTH-FACTOR IS A POTENTIAL TUMOR ANGIOGENESIS FACTOR IN HUMAN GLIOMAS INVIVO
VASCULAR ENDOTHELIAL GROWTH-FACTOR IS A POTENTIAL TUMOR ANGIOGENESIS FACTOR IN HUMAN GLIOMAS INVIVO
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DOI：
10.1038/359845a0
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发表时间：
1992-10-29
期刊：
影响因子：
64.8
通讯作者：
RISAU, W
中科院分区：
文献类型：
--
作者：
PLATE, KH;BREIER, G;RISAU, W
临床和实验研究表明，血管生成是实体瘤生长的先决条件1，2。几种生长因子在体外对内皮细胞具有促有丝分裂或趋化活性，但尚不清楚这些生长因子是否在活体中介导肿瘤血管形成3。胶质母细胞瘤是人类最常见和最恶性的脑瘤，其与星形细胞瘤的区别在于存在坏死和血管增殖5，6。在这里，我们发现血管内皮生长因子(VEGF)在星形细胞瘤细胞中诱导表达，但在两种明显不同的胶质母细胞瘤细胞亚群中显著上调。血管内皮生长因子的高亲和力酪氨酸激酶受体Flt虽然在正常脑内皮细胞中不表达，但在体内的肿瘤内皮细胞中表达上调。这些观察结果有力地支持了肿瘤血管生成受旁分泌机制调控的观点，并确认在体内VEGF是一种潜在的肿瘤血管生成因子。
CLINICAL and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth1,2. Several growth factors with mitogenic or chemotactic activity for endothelial cells in vitro have been described, but it is not known whether these mediate tumour vascularization in vivo3,4. Glioblastoma, the most common and most malignant brain tumour in humans, is distinguished from astrocytoma by the presence of necroses and vascular proliferations5,6. Here we show that expression of an endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), is induced in astrocytoma cells but is dramatically upregulated in two apparently different subsets of glioblastoma cells. The high-affinity tyrosine kinase receptor for VEGF, flt, although not expressed in normal brain endothelium, is upregulated in tumour endothelial cells in vivo. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify VEGF as a potential tumour angiogenesis factor in vivo.