title: Coexpression of EpCAM, CD44 variant isoforms and claudin-7 in anaplastic thyroid carcinoma.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Two 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
  Our 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.
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Onoda
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ashida
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Okuyama
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ito
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; C473647:CD44S antigen; C112697:CD44v6 antigen; C473255:CLDN7 protein, human; D015815:Cell Adhesion Molecules; D057167:Claudins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D020033:Protein Isoforms; D012333:RNA, Messenger; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
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