Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion
Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion
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DOI：
10.1073/pnas.0610733104
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发表时间：
2007-02-20
影响因子：
11.1
通讯作者：
Ringel, Matthew D.
中科院分区：
文献类型：
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作者：
Vasko, Vasily;Espinosa, Allan V.;Ringel, Matthew D.
甲状腺乳头状癌（PTC）侵入局部结构与预后不良有关，但PTC侵入的机制尚未完全确定，限制了新疗法的发展。为了表征参与PTC侵袭的生物学过程，我们通过寡核苷酸微阵列分析了来自7个广泛侵袭性PTC和正常甲状腺组织的中央和侵袭性区域的显微镜下解剖的瘤内样本的基因表达谱，并进行了确证性表达和功能研究。与原发性PTC的中心区域相比，侵袭性前沿过表达TGF β、NF kappa B和整联蛋白途径成员以及小G蛋白和CDC 42的调节因子。此外，降低水平的mRNA编码的蛋白质参与细胞间粘附和通信被确定，与上皮细胞间质转化（EMT）。为了证实侵袭性PTC的特征在于EMT，检查了另外34个PTC的波形蛋白表达，波形蛋白是EMT的标志。vimentin的过表达与PTC浸润和淋巴结转移有关。体外功能研究表明，波形蛋白是甲状腺癌细胞间充质形态和侵袭力的发展和维持所必需的。我们的结论是，EMT是常见的PTC的侵袭和波形蛋白调节甲状腺癌EMT在体外。
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, NF kappa B 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.