Tumor induction of VEGF promoter activity in stromal cells
Tumor induction of VEGF promoter activity in stromal cells
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DOI：
10.1016/s0092-8674(00)81731-6
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发表时间：
1998-09-18
期刊：
影响因子：
64.5
通讯作者：
Seed, B
中科院分区：
文献类型：
--
作者：
Fukumura, D;Xavier, R;Seed, B
在血管内皮生长因子（VEGF）启动子的控制下，建立了表达维多利亚绿荧光蛋白（GFP）的转基因小鼠系。携带转基因的小鼠在愈合边缘周围和浅表溃疡性伤口的肉芽组织中显示出绿色的细胞荧光。在转基因小鼠体内植入实体瘤后，由于肿瘤诱导宿主VEGF启动子活性，导致绿色荧光积累。随着时间的推移，荧光细胞侵入肿瘤，可以在整个肿瘤肿块中看到。癌基因表达诱导的自发性乳腺肿瘤在VEGF-GFP小鼠中表现出较强的间质性而非肿瘤性GFP表达。在伤口和肿瘤模型中，主要的gfp阳性细胞是成纤维细胞。非转化细胞的VEGF启动子被肿瘤微环境强烈激活的发现表明需要分析和理解肿瘤血管生成中的基质细胞协同作用。
We have established a line of transgenic mice expressing the A. victoria green fluorescent protein (GFP) under the control of the promoter for vascular endothelial growth factor (VEGF). Mice bearing the transgene show green cellular fluorescence around the healing margins and throughout the granulation tissue of superficial ulcerative wounds. Implantation of solid tumors in the transgenic mice leads to an accumulation of green fluorescence resulting from tumor induction of host VEGF promoter activity. With time, the fluorescent cells invade the tumor and can be seen throughout the tumor mass. Spontaneous mammary tumors induced by oncogene expression in the VEGF-GFP mouse show strong stromal, but not tumor, expression of GFP. In both wound and tumor models the predominant GFP-positive cells are fibroblasts. The finding that the VEGF promoter of nontransformed cells is strongly activated by the tumor microenvironment points to a need to analyze and understand stromal cell collaboration in tumor angiogenesis.