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同基因肺腺癌细胞原位移植以研究程序性死亡受体配体1(PD-L1)表达

Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression.

作者信息

Moll Herwig P, Mohrherr Julian, Breitenecker Kristina, Haber Marcel, Voronin Viktor, Casanova Emilio

机构信息

Department of Physiology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna;

Ludwig Boltzmann Institute for Cancer Research (LBI-CR).

出版信息

J Vis Exp. 2019 Jan 19(143). doi: 10.3791/58101.

Abstract

The use of mouse models is indispensable for studying the pathophysiology of various diseases. With respect to lung cancer, several models are available, including genetically engineered models as well as transplantation models. However, genetically engineered mouse models are time-consuming and expensive, whereas some orthotopic transplantation models are difficult to reproduce. Here, a non-invasive intratracheal delivery method of lung tumor cells as an alternative orthotopic transplantation model is described. The use of mouse lung adenocarcinoma cells and syngeneic graft recipients allows studying tumorigenesis under the presence of a fully active immune system. Furthermore, genetic manipulations of tumor cells before transplantation makes this model an attractive time-saving approach to study the impact of genetic factors on tumor growth and tumor cell gene expression profiles under physiological conditions. Using this model, we show that lung adenocarcinoma cells express increased levels of the T-cell suppressor programmed death-ligand 1 (PD-L1) when grown in their natural environment as compared to cultivation in vitro.

摘要

小鼠模型对于研究各种疾病的病理生理学不可或缺。就肺癌而言,有多种模型可供使用,包括基因工程模型以及移植模型。然而,基因工程小鼠模型耗时且昂贵,而一些原位移植模型难以重复。在此,描述了一种作为替代原位移植模型的非侵入性气管内递送肺肿瘤细胞的方法。使用小鼠肺腺癌细胞和同基因移植受体能够在完全活跃的免疫系统存在的情况下研究肿瘤发生。此外,移植前对肿瘤细胞进行基因操作使该模型成为一种有吸引力的省时方法,可用于研究生理条件下遗传因素对肿瘤生长和肿瘤细胞基因表达谱的影响。利用该模型,我们发现与体外培养相比,肺腺癌细胞在其自然环境中生长时,T细胞抑制因子程序性死亡配体1(PD-L1)的表达水平升高。

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