A novel eGFP-expressing immunodeficient mouse model to study tumor-host interactions

A novel eGFP-expressing immunodeficient mouse model to study tumor-host interactions
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DOI:
10.1096/fj.08-109611
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发表时间:
2008-09-01
期刊:
影响因子:
4.8
通讯作者:
Bjerkvig, Rolf
Bjerkvig, Rolf
中科院分区:
生物学2区
文献类型:
--
作者:
Niclou, Simone P.;Danzeisen, Claude;Bjerkvig, Rolf

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描述了表达增强绿色荧光蛋白(eGFP)的NOD/Scid小鼠,其中人类和小鼠肿瘤标记为红色荧光蛋白,可以在体内皮下和原位位置建立。利用光学显微镜和多光子共聚焦显微镜技术,我们详细地观察了肿瘤和宿主细胞在原位的复杂共定位。此外,利用荧光激活细胞分选(FACS),我们能够将宿主细胞与肿瘤细胞完全分离,从而为肿瘤-宿主细胞相互作用的详细细胞和分子分析提供了一个系统。肿瘤和宿主细胞可以可靠地识别,这一事实也使我们能够检测可能由细胞融合事件或水平基因转移引起的双阳性细胞。同样,该模型可用于循环转移细胞的检测和肿瘤内血管室的详细研究,包括血管生成模拟。因此,所描述的模型应该为肿瘤细胞如何与其微环境通信提供重要的见解。
A NOD/Scid mouse expressing enhanced green fluorescent protein (eGFP) is described, in which human and mouse tumors marked with red fluorescent protein can be established in vivo, both at subcutaneous and orthotopic locations. Using light microscopy as well as multiphoton confocal microscopy techniques, we visualized in detail the intricate colocalization of tumor and host cells in situ. Moreover, using fluorescence-activated cell sorting (FACS), we were able to completely separate the host cells from the tumor cells, thus providing a system for detailed cellular and molecular analysis of tumor-host cell interactions. The fact that tumor and host cells can be reliably identified also allowed us to detect double-positive cells, possibly arising from cell fusion events or horizontal gene transfer. Similarly, the model can be applied for the detection of circulating metastatic cells and for detailed studies on the vascular compartments within tumors, including vasculogenic mimicry. Thus, the model described should provide significant insight into how tumor cells communicate with their microenvironment.