Fukumura D, Xavier R, Sugiura T, Chen Y, Park E C, Lu N, Selig M, Nielsen G, Taksir T, Jain R K, Seed B
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Cell. 1998 Sep 18;94(6):715-25. doi: 10.1016/s0092-8674(00)81731-6.
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.
我们构建了一种转基因小鼠品系，该品系在血管内皮生长因子（VEGF）启动子的控制下表达维多利亚多管发光水母绿色荧光蛋白（GFP）。携带转基因的小鼠在浅表溃疡性伤口的愈合边缘及整个肉芽组织周围呈现绿色细胞荧光。在转基因小鼠体内植入实体瘤会导致宿主VEGF启动子活性被肿瘤诱导，从而积累绿色荧光。随着时间推移，荧光细胞侵入肿瘤并可见于整个肿瘤块中。在VEGF-GFP小鼠中，由癌基因表达诱导的自发性乳腺肿瘤显示GFP在基质中有强烈表达，但肿瘤中无表达。在伤口和肿瘤模型中，主要的GFP阳性细胞均为成纤维细胞。未转化细胞的VEGF启动子被肿瘤微环境强烈激活这一发现表明，有必要分析和了解肿瘤血管生成中基质细胞的协作情况。
