Department of Medicine, Indiana University School of Medicine, Walther Hall, 980W Walnut Street, C230, IN 46202, USA.
Lab Invest. 2012 Nov;92(11):1564-73. doi: 10.1038/labinvest.2012.115. Epub 2012 Aug 27.
Thymomas are low-grade epithelial tumors of the anterior mediastinum. The complexity of the disease and the lack of in vitro and in vivo models hamper the development of better therapeutics. In this study, we report a novel cell line, designated as IU-TAB-1, which was established from a patient with stage II thymoma (World Health Organization-type AB). The IU-TAB-1 cell line was established in vitro and characterized using histological and immunohistochemical staining, fluorescence-activated cell sorting, cytogenetic analyses and functional assays including in vitro and a NOD/SCID xenograft model. A whole-genome gene expression analysis (Illumina) was performed on the IU-TAB-1 cell line and 34 thymomas to determine the clinical relevance of the cell line. The IU-TAB-1 cell line was positive for epithelial markers (pan-cytokeratin and EpCAM/CD326) including thymic epithelial (TE) surface markers (such as CD29, CD9, CD54/ICAM-1, CD58 and CD24) and p63, and negative for B- and T-cell lineage markers. Gene expression profiling demonstrated overlapping and distinct genes between IU-TAB-1 and primary thymomas including the primary tumor (from which the cell line was derived). IU-TAB-1 cells are tumorigenic when implanted in immunodeficient mice with tumors reaching a volume of 1000 mm³ at around 130 days. The established cell line represents a biologically relevant new tool to investigate the molecular pathology of thymic malignancies and to evaluate the efficacy of novel therapeutics both in vitro and in vivo.
胸腺瘤是前纵隔的低级别上皮性肿瘤。该疾病的复杂性以及缺乏体外和体内模型,阻碍了更好治疗方法的发展。在本研究中,我们报告了一种新型细胞系,命名为 IU-TAB-1,它是从 II 期胸腺瘤(世界卫生组织 AB 型)患者中建立的。IU-TAB-1 细胞系在体外建立并通过组织学和免疫组织化学染色、荧光激活细胞分选、细胞遗传学分析和包括体外和 NOD/SCID 异种移植模型在内的功能测定进行了表征。对 IU-TAB-1 细胞系和 34 例胸腺瘤进行了全基因组基因表达分析(Illumina),以确定细胞系的临床相关性。IU-TAB-1 细胞系表达上皮标志物(泛细胞角蛋白和 EpCAM/CD326),包括胸内上皮(TE)表面标志物(如 CD29、CD9、CD54/ICAM-1、CD58 和 CD24)和 p63,并且为 B 细胞和 T 细胞谱系标志物阴性。基因表达谱分析表明,IU-TAB-1 和原发性胸腺瘤(包括原肿瘤,细胞系即由此衍生)之间存在重叠和独特的基因。当将 IU-TAB-1 细胞系植入免疫缺陷小鼠中时,肿瘤会发生肿瘤发生,在大约 130 天时肿瘤体积达到 1000mm³。该建立的细胞系代表了一种具有生物学相关性的新工具,可用于研究胸内恶性肿瘤的分子病理学,并评估新型治疗方法在体外和体内的疗效。