School of Medicine, IRIBHM, Université Libre de Bruxelles Brussels, Belgium.
Front Endocrinol (Lausanne). 2012 Nov 16;3:133. doi: 10.3389/fendo.2012.00133. eCollection 2012.
Human thyroid cancer cell lines are the most used models for thyroid cancer studies. They must be used with detailed knowledge of their characteristics. These in vitro cell lines originate from differentiated and dedifferentiated in vivo human thyroid tumors. However, it has been shown that mRNA expression profiles of these cell lines were closer to dedifferentiated in vivo thyroid tumors (anaplastic thyroid carcinoma, ATC) than to differentiated ones. Here an overview of the knowledge of these models was made. The mutational status of six human thyroid cancer cell lines (WRO, FTC133, BCPAP, TPC1, K1, and 8505C) was in line with previously reported findings for 10 genes frequently mutated in thyroid cancer. However, the presence of a BRAF mutation (T1799A: V600E) in WRO questions the use of this cell line as a model for follicular thyroid carcinoma (FTC). Next, to investigate the biological meaning of the modulated mRNAs in these cells, a pathway analysis on previously obtained mRNA profiles was performed on five cell lines. In five cell lines, the MHC class II pathway was down-regulated and in four of them, ribosome biosynthesis and translation pathways were up-regulated. mRNA expression profiles of the cell lines were also compared to those of the different types of thyroid cancers. Three datasets originating from different microarray platforms and derived from distinct laboratories were used. This meta-analysis showed a significant higher correlation between the profiles of the thyroid cancer cell lines and ATC, than to differentiated thyroid tumors (i.e., PTC or FTC) specifically for DNA replication. This already observed higher correlation was obtained here with an increased number of in vivo tumors and using different platforms. In summary, this would suggest that some papillary thyroid carcinoma or follicular thyroid carcinoma (PTC or FTC) cell lines (i.e., TPC-1) might have partially lost their original DNA synthesis/replication regulation mechanisms during their in vitro cell adaptation/evolution.
人甲状腺癌细胞系是甲状腺癌研究中最常用的模型。在使用这些模型时,必须详细了解它们的特性。这些体外细胞系源自分化和去分化的体内人甲状腺肿瘤。然而,已经表明,这些细胞系的 mRNA 表达谱与去分化的体内甲状腺肿瘤(间变性甲状腺癌,ATC)更为接近,而不是分化的肿瘤。本文综述了这些模型的相关知识。六种人甲状腺癌细胞系(WRO、FTC133、BCPAP、TPC1、K1 和 8505C)的突变状态与先前报道的甲状腺癌中 10 个常突变基因的结果一致。然而,WRO 中存在 BRAF 突变(T1799A:V600E),这使得该细胞系作为滤泡状甲状腺癌(FTC)模型的使用受到质疑。接下来,为了研究这些细胞中调节的 mRNAs 的生物学意义,对五个细胞系的先前获得的 mRNA 谱进行了途径分析。在五个细胞系中,MHC Ⅱ类途径下调,在其中四个细胞系中,核糖体生物合成和翻译途径上调。还将细胞系的 mRNA 表达谱与不同类型的甲状腺癌进行了比较。使用了三个源自不同微阵列平台和不同实验室的数据集。这项荟萃分析显示,甲状腺癌细胞系与 ATC 的谱之间的相关性显著高于与分化型甲状腺肿瘤(即 PTC 或 FTC)的相关性,特别是在 DNA 复制方面。与之前的研究相比,本研究使用了更多的体内肿瘤和不同的平台,获得了更高的相关性。综上所述,这表明一些甲状腺乳头状癌或滤泡状甲状腺癌(PTC 或 FTC)细胞系(如 TPC-1)在体外细胞适应/进化过程中,可能部分丧失了其原始的 DNA 合成/复制调控机制。