Snail-dependent and -independent epithelial-mesenchymal transition in oral squamous carcinoma cells
Snail-dependent and -independent epithelial-mesenchymal transition in oral squamous carcinoma cells
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DOI：
10.1369/jhc.6a6958.2006
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发表时间：
2006-11-01
影响因子：
3.2
通讯作者：
Virtanen, Ismo
中科院分区：
文献类型：
--
作者：
Takkunen, Minna;Grenman, Reidar;Virtanen, Ismo
E-cadherin的消失是上皮-间质转化（EMT）的一个里程碑，在癌和一些纤维化疾病中都发现了EMT。我们研究了口腔鳞状细胞癌（SCC）原发瘤（43 A）和复发瘤（43 B）细胞中EMT的机制。而来自原发性癌的细胞显示出典型的鳞状上皮细胞表型，包括E-钙粘蛋白和层粘连蛋白-332（层粘连蛋白-5），来自复发性肿瘤的细胞表达去分化的、EMT经历的肿瘤的特征。43 B细胞表达E-钙粘蛋白阻遏物ZEB-1/delta EF 1，特别是ZEB-2/SIP 1，因此它们在这些细胞中似乎是内源性EMT的候选者。用SNAIL cDNA转染43 A细胞，观察内源性和外源性EMT的差异。SNAIL转染的细胞表现出完整的EMT表型，具有成纤维细胞样外观、波形蛋白丝、E-钙粘蛋白/N-钙粘蛋白转换、缺乏半桥粒，以及作为EMT的新特征的缺乏层粘连蛋白-332合成。在这些细胞中，ZEB-1和ZEB-2的上调是明显的，表明SNAIL可以调节这些E-钙粘蛋白阻遏物。针对SNAIL的新的单克隆抗体不仅在SNAIL转染的细胞中显示核免疫反应性，而且在缺乏Lm-332的产生并显示EMT迹象的癌细胞中也显示核免疫反应性。这些结果表明，在上皮细胞分化程序和EMT在SCC细胞的变化可能会导致从几个E-钙粘蛋白阻遏物之间的相互作用，然而，SNAIL单独能够完成一个完整的EMT。
Disappearance of E-cadherin is a milestone for epithelial-mesenchymal transition (EMT), found both in carcinomas and in some fibrotic diseases. We have studied the mechanisms of EMT in oral squamous cell carcinoma (SCC) cells isolated from primary tumor (43A) and its recurrent tumor (43B). Whereas the cells from primary carcinoma displayed a typical phenotype of squamous epithelial cells including E-cadherin and laminin-332 (laminin-5), cells from recurrent tumor expressed characteristics of dedifferentiated, EMT-experienced tumors. 43B cells expressed E-cadherin repressors ZEB-1/delta EF1 and especially ZEB-2/SIP1, which therefore appear as candidates for endogenous EMT in these cells. Differences between endogenous and exogenous EMT were assessed by transfecting 43A cells with SNAIL cDNA. SNAIL-transfected cells showed complete EMT phenotype with fibroblastoid appearance, vimentin filaments, E-cadherin/N-cadherin switch, lack of hemidesmosomes and, as a new feature of EMT, lack of laminin-332 synthesis. Upregulation of ZEB-1 and ZEB-2 was evident in these cells, suggesting that SNAIL can regulate these E-cadherin repressors. New monoclonal antibodies against SNAIL showed nuclear immunoreactivity not only in the SNAIL-transfected cells but also in carcinoma cells lacking production of Lm-332 and showing signs of EMT. These results suggest that changes in the epithelial cell differentiation program and EMT in SCC cells can result from the interplay among several E-cadherin repressors; however, SNAIL alone is able to accomplish a complete EMT.