title: Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.
abstract: Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF beta, NFkappaB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.
authors.affiliation: Department of Medicine, Arthur G. James Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Vasily
authors.initials: V
authors.lastname: Vasko
authors.forename: Allan V
authors.initials: AV
authors.lastname: Espinosa
authors.forename: William
authors.initials: W
authors.lastname: Scouten
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.forename: Herbert
authors.initials: H
authors.lastname: Auer
authors.forename: Sandya
authors.initials: S
authors.lastname: Liyanarachchi
authors.forename: Alexander
authors.initials: A
authors.lastname: Larin
authors.forename: Victoria
authors.initials: V
authors.lastname: Savchenko
authors.forename: Gary L
authors.initials: GL
authors.lastname: Francis
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Saji
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008648:Mesoderm / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014746:Vimentin