Human Thyroid Tumor Cell Lines Derived from Different Tumor Types Present a Common Dedifferentiated Phenotype

Abstract

Cell lines are crucial to elucidate mechanisms of tumorigenesis and serve as tools for cancer treatment screenings. Therefore, careful validation of whether these models have conserved properties of in vivo tumors is highly important. Thyrocyte-derived tumors are very interesting for cancer biology studies because from one cell type, at least five histologically characterized different benign and malignant tumor types can arise. To investigate whether thyroid tumorderived cell lines are representative in vitro models, characteristics of eight of those cell lines were investigated with microarrays, differentiation markers, and karyotyping. Our results indicate that these cell lines derived from differentiated and undifferentiated tumor types have evolved in vitro into similar phenotypes with gene expression profiles the closest to in vivo undifferentiated tumors. Accordingly, the absence of expression of most thyrocyte-specific genes, the nonresponsiveness to thyrotropin, as well as their large number of chromosomal abnormalities, suggest that these cell lines have acquired characteristics of fully dedifferentiated cells. They represent the outcome of an adaptation and evolution in vitro, which questions the reliability of these cell lines as models for differentiated tumors. However, they may represent useful models for undifferentiated cancers, and by their comparison with differentiated cells, can help to define the genes involved in the differentiation/dedifferentiation process. The use of any cell line as a model for a cancer therefore requires prior careful and thorough validation for the investigated property. [Cancer Res 2007;67(17):8113-20]

The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type

“…Our findings regarding the SNP in chromosome 14q13.3 would seem to pinpoint a prototype noncoding regulatory RNA gene. The suppression of PTCSC3 in thyroid tumor tissue of PTC patients and the lack of its expression in PTC cell line cells that show features of poorly differentiated thyroid cancer (27) suggest that PTCSC3 expression is lost when the normal thyroid tissue de-differentiates into cancer. Our data demonstrate that restoration of PTCSC3 expression in TPC-1 and BCPAP cells inhibits cell growth suggesting that PTCSC3 has tumor suppressor properties.…”

Potential Utility and Limitations of Thyroid Cancer Cell Lines as Models for Studying Thyroid Cancer

“…Recently, both redundancy among thyroid cancer cell lines with different names and misidentification of cell lines as thyroid cancer cells that are not of thyroid origin have been reported (10)(11)(12). For example, PTC-derived BHP2-7, BHP10-3, BHP7-13, FB2, and TPC1 cell lines have been shown to be genetically identical to each other as well as K1 and K2 (10,11).…”

“…Maenhaut and coworkers have also determined the expression levels of other thyroid-specific genes such as ThOX2 (12). Although they failed to detect ThOX2 expression in the eight investigated cell lines, they found weak expression of a related gene ThOX1 in BCPAP cells.…”

“…The FTC-derived cell lines such as FTC133 and WRO82-1 are known to express the thyroidspecific transcription factors PAX8 and TTF-1; in addition, the WRO82-1 cells also express TTF-2, albeit to a lesser extent, but fail to show the expression of other thyroid markers such as TSH-R, NIS, Tg, TPO, THOX1, and THOX2 (10,11,12).…”

“…An extensive karyotype description has been reported only for the FTC133 and WRO82-1 cell lines (12,21,28). In particular, the FTC133 cells revealed significant gains in part or whole of chromosomes 1,11,6,7,8,14,15,19, and 20, and losses in chromosomes 16, 21, and 22 (28).…”