Holtkamp Nikola, Afanasieva Anastasia, Elstner Anja, van Landeghem Frank K H, Könneker Matthias, Kuhn Susanne A, Kettenmann Helmut, von Deimling Andreas
Institute of Neuropathology, Charité Universitätsmedizin Berlin, Germany.
Biochem Biophys Res Commun. 2005 Nov 4;336(4):1227-33. doi: 10.1016/j.bbrc.2005.08.253.
Invasion of tumor cells into adjacent brain areas is one of the major problems in treatment of glioma patients. To identify genes that might contribute to invasion, fluorescent F98 glioma cells were allowed to invade an organotypic brain slice. Gene expression analysis revealed 5 up-regulated and 14 down-regulated genes in invasive glioma cells as compared to non-invasive glioma cells. Two gene products, ferritin and cyclin B1, were verified in human gliomas by immunohistochemistry. Ferritin exhibited high mRNA levels in migratory F98 cells and also showed higher protein expression in the infiltrating edge of human gliomas. Cyclin B1 with high mRNA expression levels in stationary F98 cells showed marked protein expression in the central portions of gliomas. These findings are compatible with the concept of tumor cells either proliferating or migrating. Our study is the first to apply brain slice cultures for the identification of differentially regulated genes in glioma invasion.
肿瘤细胞侵入邻近脑区是胶质瘤患者治疗中的主要问题之一。为了鉴定可能促成侵袭的基因，使荧光F98胶质瘤细胞侵袭器官型脑片。基因表达分析显示，与非侵袭性胶质瘤细胞相比，侵袭性胶质瘤细胞中有5个基因上调，14个基因下调。通过免疫组织化学在人胶质瘤中验证了两种基因产物，即铁蛋白和细胞周期蛋白B1。铁蛋白在迁移的F98细胞中表现出高mRNA水平，并且在人胶质瘤的浸润边缘也显示出更高的蛋白表达。在静止的F98细胞中具有高mRNA表达水平的细胞周期蛋白B1在胶质瘤的中央部分显示出明显的蛋白表达。这些发现与肿瘤细胞增殖或迁移的概念相符。我们的研究首次应用脑片培养来鉴定胶质瘤侵袭中差异调节的基因。
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