Abstract
BackgroundAnaplastic thyroid cancer is considered to be one of the most aggressive human malignancies, and the mean survival time after diagnosis is approximately six months, regardless of treatments. This study aimed to examine how EpCAM and its related molecules are involved in the characteristics of anaplastic thyroid carcinoma.Methodology/Principal FindingsTwo differentiated thyroid cancer cell lines (TPC-1 and FTC-133), and two anaplastic thyroid cancer cell lines (FRO, ACT-1) were analyzed for expression of CD44 standard isoform (CD44s), CD44 variant isoforms, and EpCAM, and human aldehyde dehydrogenase-1 (ALDH1) enzymatic activity using flow cytometry. CD44s expression was higher in TPC-1 and FTC-133 than in the FRO and ACT-1, whereas ALDH1 activities were higher in FRO and ACT-1 than in TPC-1 and FTC-133. An inverse correlation between CD44s expression and ALDH1 activity was observed in all thyroid cancer cell lines. As for the expressions of CD44 variant isoforms, ACT-1 showed higher and FRO showed moderate CD44v6 expressions, whereas either TPC-1 or FTC-133 showed negative CD44v6 expression. EpCAM expressions in FRO and ACT-1 were higher than those in TPC-1 and FTC-133, and EpCAM expressions inversely correlated with those of CD44s. A positive correlation was observed between EpCAM expression and ALDH1 activity in thyroid cancer cell lines. In the RT-PCR analysis, the expression levels of EpCAM, caludin-7 and ALDH1 in FRO and ATC-1 cells were significantly higher than those in TPC-1 and FTC-133 cells. In clinical specimens of thyroid cancers, nuclear expression of EpCAM and high expression of CD44v6 were detected significantly more frequently in anaplastic carcinomas.Conclusions/SignificanceOur study suggests the possibility that EpCAM, together with CD44v6 and claudin-7 as well as ALDH1, may be involved in the development of the aggressive phenotype of anaplastic thyroid carcinoma. Our findings may suggest a novel therapeutic strategy for treatment of anaplastic thyroid carcinoma.
Highlights
Thyroid cancer is the most common endocrine malignancy worldwide as well as in Japan
Epithelial cell adhesion molecule (EpCAM) and CD44 standard isoform (CD44s) were inversely expressed in these four cell lines, with the anaplastic thyroid cancer cell lines expressing higher levels of EpCAM and lower levels of CD44s compared with the differentiated cancer cell lines
We demonstrated that EpCAM, together with CD44 and claudin-7, is associated with the phenotype of anaplastic thyroid cancer both in the established cell lines and clinical specimens
Summary
Thyroid cancer is the most common endocrine malignancy worldwide as well as in Japan. Thyroid carcinomas are classified into the following four representative histological types: papillary, follicular, medullary, and anaplastic carcinomas. Medullary carcinoma derives from thyroid parafollicular (neuroendocrine) C cells, whereas papillary, follicular, and anaplastic carcinomas originate from thyroid follicular cells. Papillary and follicular carcinomas together are termed as differentiated thyroid carcinomas, and they generally carry a favorable prognosis. Anaplastic thyroid cancer is considered to be one of the most virulent human malignancies and the mean survival time after diagnosis is less than one year, regardless of the treatment administered [1,2,3]. Anaplastic thyroid cancer is considered to be one of the most aggressive human malignancies, and the mean survival time after diagnosis is approximately six months, regardless of treatments. This study aimed to examine how EpCAM and its related molecules are involved in the characteristics of anaplastic thyroid carcinoma
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