Mischek Daniela, Steinborn Ralf, Petznek Helga, Bichler Christoph, Zatloukal Kurt, Stürzl Michael, Günzburg Walter H, Hohenadl Christine
Department of Pathobiology, Institute of Virology, University of Veterinary Medicine, Vienna, Austria.
J Biomed Biotechnol. 2009;2009:437284. doi: 10.1155/2009/437284. Epub 2009 Mar 15.
To develop and evaluate new therapeutic strategies for the treatment of human cancers, well-characterised preclinical model systems are a prerequisite. To this aim, we have established xenotransplantation mouse models and corresponding cell cultures from surgically obtained secondary human liver tumours. Established xenograft tumours were patho- and immunohistologically characterised, and expression levels of cancer-relevant genes were quantified in paired original and xenograft tumours and the derivative cell cultures applying RT-PCR-based array technology. Most of the characteristic morphological and immunohistochemical features of the original tumours were shown to be maintained. No differences were found concerning expression of genes involved in cell cycle regulation and oncogenesis. Interestingly, cytokine and matrix metalloproteinase encoding genes appeared to be expressed differentially. Thus, the established models are closely reflecting pathohistological and molecular characteristics of the selected human tumours and may therefore provide useful tools for preclinical analyses of new antitumour strategies in vivo.
为了开发和评估治疗人类癌症的新治疗策略,特征明确的临床前模型系统是先决条件。为此,我们从手术获取的继发性人类肝肿瘤中建立了异种移植小鼠模型及相应的细胞培养物。对已建立的异种移植肿瘤进行了病理和免疫组织学特征分析,并应用基于逆转录-聚合酶链反应(RT-PCR)的芯片技术,对配对的原发肿瘤和异种移植肿瘤以及衍生的细胞培养物中癌症相关基因的表达水平进行了定量分析。结果显示,原发肿瘤的大多数特征性形态和免疫组化特征得以保留。在细胞周期调控和肿瘤发生相关基因的表达方面未发现差异。有趣的是,细胞因子和基质金属蛋白酶编码基因的表达似乎存在差异。因此,所建立的模型密切反映了所选人类肿瘤的病理组织学和分子特征,可为体内新抗肿瘤策略的临床前分析提供有用工具。