Thyroid cancer cell lines: an overview

Abstract

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.

Keywords: BCPAP; FTC133; TPC1; WRO; cancer; cell line; mutation; thyroid.

Figure 1

(A) Sequence of BRAF in WRO cells. The arrow shows the T1799A mutation. (B) Sequence of PI3KCA in K1 cells. The arrow indicates the G1624A mutation.

Figure 2

Boxplots of correlations between cell lines and in vivo thyroid tumors. (A and B) Correlations were calculated based on 2,392 mRNA expressions comparing human thyroid cancer cell lines (CL) with different types of in vivo human thyroid tumors by using three datasets. The first was composed of five thyroid cancer cell lines (WRO, FTC133, BCPAP, TPC1, 8505C) hybridized on IRIBHM custom slides. The second was composed of 11 ATC and 49 PTC hybridized on Affymetrix HG U133 Plus 2.0 (A). The third was composed of 4 ATC, 13 FTC, and 51 PTC hybridized on Affymetrix HG U133A (B). P-values indicate whether ATC and cell lines had more similar profiles than FTC or PTC and cell lines. P-values were significant for both independent datasets. (C) 2D-multidimensional scaling representation of the mRNA expression profiles of cell lines, ATC, PTC, and FTC based on 2392 mRNA expressions.

Figure 3

Heatmap of 145 mRNA expressions in thyroid cancer cell lines (CL) and in human thyroid tumors. These genes were the most commonly up and down-regulated genes in ATC and in the cell lines. The level of modulation of these genes in PTC and FTC are also shown. Profiles of the five cell lines are underlined in black. Profiles of the samples hybridized on Affymetrix HG U133 Plus 2.0 platform and on Affymetrix HG U133A platform are underlined in blue and violet respectively. Genes are indicated by their official gene symbols.