Involvement of epithelial-mesenchymal transition in adenoid cystic carcinoma metastasis
Involvement of epithelial-mesenchymal transition in adenoid cystic carcinoma metastasis
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DOI：
10.3892/ijo.2011.917
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发表时间：
2011-04-01
影响因子：
5.2
通讯作者：
Shirasuna, Kanemitsu
中科院分区：
文献类型：
--
作者：
Ishii, Kotaro;Shimoda, Miyuki;Shirasuna, Kanemitsu
高频率的复发和远处转移的腺样囊性癌（AdCC）的患者的长期治愈的显着障碍，并强调需要更好地了解与这些结果相关的生物学因素。为了鉴定介导AdCC转移的蛋白质，我们在裸鼠中使用原位移植和体内选择从ACCS细胞系建立了三种表达绿色荧光蛋白（GFP）的AdCC细胞系：亲本ACCS-GFP、高致瘤性ACCS-T GFP和转移性ACCS-M GFP。对ACCS-GFP和ACCS-M GFP进行DNA微阵列分析，结果用于数据挖掘研究。DNA微阵列分析揭示了ACC-M GFP细胞中显著改变的生物学过程，包括与细胞粘附（三类）和信号传导（三类）相关的事件。特别是，观察到细胞粘附分子（例如钙粘蛋白和整合素亚基）显着下调。免疫印迹证实ACCS-M GFP细胞中E-钙粘蛋白和整合素的丢失和波形蛋白的获得。这些结果表明，上皮间质转化（EMT）是一个假定的事件，在AdCC转移，诱导肿瘤细胞从原发肿瘤部位的传播。总之，在本研究中，我们建立了一个有用的裸鼠转移模型，这将使进一步的AdCC转移研究和临床治疗试验，我们也提供了证据，EMT是显着参与AdCC转移过程。
The high frequencies of recurrence and distant metastasis of adenoid cystic carcinoma (AdCC) are significant obstacles for the long-term cure of patients with AdCC and emphasize the need for better understanding of the biological factors associated with these outcomes. To identify proteins that mediate AdCC metastasis, we established three AdCC cell lines expressing green fluorescent protein (GFP) from the ACCS cell line using orthotopic transplantation and in vivo selection in nude mice: Parental ACCS-GFP, highly tumorigenic ACCS-T GFP and metastatic ACCS-M GFP. ACCS-GFP and ACCS-M GFP were subjected to DNA microarray analysis and the results were used for data mining studies. DNA microarray analysis revealed significantly altered biological processes in the ACC-M GFP cells, including events related to cell adhesion (three categories) and signaling (three categories). In particular, a significant down-regulation of cell adhesion molecules, such as cadherins and integrin subunits was observed. The loss of E-cadherin and integrins and the gain of vimentin in ACCS-M GFP cells were confirmed by immunoblotting. These results suggest that epithelial-mesenchymal transition (EMT) is a putative event in AdCC metastasis that induces tumor cell dissemination from the primary tumor site. In summary, in this study we established a useful nude mouse metastasis model which will enable further AdCC metastasis research and clinical treatment trials and we also provide evidence that EMT is significantly involved in the AdCC metastatic process.