The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, China.
Department of Pathology, Affiliated Hospital of Jining Medical University, Jining, 272029, Shandong, China.
Mol Cell Biochem. 2018 Jan;438(1-2):47-57. doi: 10.1007/s11010-017-3112-z. Epub 2017 Jul 25.
Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, with tendency to spread to regional lymph nodes and distant organs at early stage. Vimentin, a major cytoskeletal protein constituent of the intermediate filament, plays a critical role in the epithelial-mesenchymal transition. Overexpression of vimentin is considered to be a critical prerequisite for metastasis in numerous human cancers. Therefore, targeting vimentin for cancer therapy has gained a lot of interest. In the present study, we detected vimentin expression in NPC tissues and found that overexpression of vimentin is associated with poor prognosis of NPC patients. Silencing of vimentin in NPC CNE2 cells by RNAi suppresses cells migration and invasion in vitro. However, blocking vimentin did not affect cell proliferation of CNE2 cells. In addition, the in vivo metastatic potential of CNE2 cells transfected with Vimentin shRNA was suppressed in a nude mouse model of pulmonary metastasis. Silencing of Vimentin in CNE2 cells leads to a decrease of microvessel density and VEGF, CD31, MMP2, and MMP9 expressions in pulmonary metastatic tumors. Importantly, we found that it is easier for the tumor cells from the high vimentin-expressing pulmonary metastatic tumors to reinvade the microvessel and to form stable tumor plaques attached to the endothelial cells, which resemble the resource of circulating tumor cells and are very hard to eliminate. However, depletion of vimentin inhibits the formation of vascular tumor plaques. Our findings suggest that RNAi-based vimentin silencing may be a potential and promising anti-metastatic therapeutic strategy for NPC.
鼻咽癌(NPC)是一种独特的头颈部癌症亚型,具有早期向局部淋巴结和远处器官转移的倾向。波形蛋白是细胞骨架蛋白中间丝的主要组成部分,在上皮-间充质转化中发挥着关键作用。在许多人类癌症中,波形蛋白的过度表达被认为是转移的关键前提。因此,针对波形蛋白进行癌症治疗引起了广泛关注。在本研究中,我们检测了 NPC 组织中的波形蛋白表达,发现波形蛋白的过表达与 NPC 患者的不良预后相关。在 NPC CNE2 细胞中通过 RNAi 沉默波形蛋白可抑制细胞的体外迁移和侵袭。然而,阻断波形蛋白并不影响 CNE2 细胞的增殖。此外,在裸鼠肺转移模型中,转染 Vimentin shRNA 的 CNE2 细胞的转移潜能受到抑制。在 CNE2 细胞中沉默 Vimentin 导致肺转移瘤中的微血管密度以及 VEGF、CD31、MMP2 和 MMP9 的表达降低。重要的是,我们发现来自高表达波形蛋白的肺转移瘤的肿瘤细胞更容易重新侵入微血管并形成附着在内皮细胞上的稳定肿瘤斑块,这类似于循环肿瘤细胞的来源,并且很难消除。然而,消耗波形蛋白可抑制血管肿瘤斑块的形成。我们的研究结果表明,基于 RNAi 的波形蛋白沉默可能是 NPC 的一种有潜力和有前途的抗转移治疗策略。