Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-02, Vol.104 (8), p.2803-2808
• Main Authors: Vasko, Vasily, Espinosa, Allan V, Scouten, William, He, Huiling, Auer, Herbert, Liyanarachchi, Sandya, Larin, Alexander, Savchenko, Victoria, Francis, Gary L, de la Chapelle, Albert, Saji, Motoyasu, Ringel, Matthew D
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Papillary - genetics; Adenocarcinoma, Papillary - pathology; Biological Sciences; Cancer; Cell lines; Cell Nucleus - metabolism; Cellular immunity; Cluster Analysis; Epithelial Cells - pathology; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic mutation; Humans; Mesoderm - pathology; Messenger RNA; Neoplasm Invasiveness; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Phosphorylation; Protein Transport; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Small interfering RNA; Thyroid cancer; Thyroid gland; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Tissue samples; Tumor Cells, Cultured; Tumors; Vimentin; Vimentin - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0610733104

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 β, NFκB 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.