Vimentin核表达在鼻咽癌中的功能鉴定及其分子机制初步研究

Our previous findings have showed that: ① Neoplastic spindle cells are particularly at the leading edge, or migrating into the surrounding stroma, and these tumor cells generate features of epithelial-mesenchymal transition (EMT); ② upregulation of nuclear vimentin expression is found in NPC compared with non-cancerous nasopharyngeal tissues, predominantly in neoplastic spindle cells, and correlate significantly with tumor metastasis and poor survival of patients. ③ NPC cell line C666-1 with high metastasic ability and spindle-shaped morphology shows high expression of nuclear vimentin, whereas it is absent in normal NPC cell line NP69. These results suggest that nuclear vimentin might be crucial for NPC growth, invasion and metastasis. We firstly want to construct stable nuclear vimentin overexpressed NPC cells, and then to investigate its impacts on tumor growth, morphology, invasion and metastasis of NPC in vivo and in vitro compared to control cells. Affymetrix genome-wide expression profile microarray and Ettan DIGE protein analysis system are used to determine the differential expression of gene and protein between the groups of stable nuclear vimentin cells and control cells , respectively.Our observations might clarify the impact of nuclear vimentin on the ability of NPC proliferation, migration and metastasis, and also provide novel views for the development and progression of NPC.

我们前期研究结果显示：①鼻咽癌肿瘤侵袭边缘及侵犯间质中的梭形癌细胞具有上皮间质转化（EMT）特征；②Vimentin在鼻咽癌组织中核表达异常升高，尤以梭形癌细胞表达明显，且其表达水平与鼻咽癌的转移和预后密切相关。③高转移性梭形鼻咽癌C666-1细胞vimentin核表达显著，正常上皮细胞表达缺失。以上结果提示vimentin核表达很可能在鼻咽癌的生长、侵袭和转移中发挥了重要作用。为此，我们拟建立稳定过表达核vimentin基因的鼻咽癌细胞系，在细胞和动物水平比较导入vimentin核表达前后对鼻咽癌细胞生长、细胞形态以及侵袭和转移的影响。利用全人类基因组芯片和荧光差异蛋白表达分析系统分别研究核vimentin基因导入前后所引起基因和蛋白表达差异，寻找其介导的重要信号转导通路。本研究将阐明vimentin核表达对鼻咽癌生长、侵袭和转移等生物学特性的影响，为鼻咽癌的发生发展提供新的认识。

我们前期研究结果显示Vimentin在鼻咽癌组织中核表达异常升高，且其蛋白表达与鼻咽癌患者的转移和预后密切相关, 提示vimentin核表达很可能在鼻咽癌的生长、侵袭和转移中发挥了重要作用。本课题主要就vimentin核表达对鼻咽癌生生物学特性的影响及其相关调控机制进行探讨。我们的结果表明，Viemtnin核表达对鼻咽癌细胞生长和细胞周期有一定的影响，可促进细胞生长和增强细胞运动侵袭力。FOXM1与Vimentin成正相关，可促进其蛋白表达核移位。本研究初步阐明vimentin核表达对鼻咽癌生长、侵袭等生物学特性的影响以及上游调控机制，为鼻咽癌的发生发展提供新的认识。