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CD147介导转化生长因子-β1诱导的舌鳞状细胞癌上皮-间质转化和细胞侵袭。

CD147 mediates transforming growth factor-β1-induced epithelial-mesenchymal transition and cell invasion in squamous cell carcinoma of the tongue.

作者信息

Suzuki Shinsuke, Toyoma Satoshi, Tsuji Tadahiro, Kawasaki Yohei, Yamada Takechiyo

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Akita University Graduate School of Medicine, Akita 010-8543, Japan.

出版信息

Exp Ther Med. 2019 Apr;17(4):2855-2860. doi: 10.3892/etm.2019.7230. Epub 2019 Jan 31.

Abstract

Epithelial-mesenchymal transition (EMT) is a physiological process in which epithelial cells attain the motile and invasive characteristics of mesenchymal cells, which results in the development of increased migratory and invasive cell behavior, serving as a vital mechanism of cancer progression. Hence, controlling the EMT for cancer treatment, including head and neck squamous cell carcinoma (HNSCC), is imperative. Among EMT-associated factors, transforming growth factor-β (TGF-β) is a well-established potent inducer. Recent research has revealed that CD147, a member of the immunoglobulin superfamily, promotes the EMT. However, the role of CD147 in the EMT and the following tumorigenicity in HNSCC has not been completely elucidated. This study aims to investigate the role of CD147 in the EMT and related tumorigenicity in HNSCC. The present study used two HNSCC cell lines, SAS and FaDu, for studies. In HNSCC cells, TGF-β1 induced spindle-shaped morphological changes, and western blot analysis revealed that TGF-β1 induced changes in EMT markers, downregulation of vimentin, and upregulation of E-cadherin, yet increased CD147. In addition, TGF-β1 increased cell migration in HNSCC cells. However, a TGF-β1-induced alteration in EMT makers was attenuated with CD147 silencing by small interfering RNA (siRNA) in SAS cells. In addition, the TGF-β1-induced cell invasion of SAS was attenuated with CD147 silencing. In conclusion, the present study suggests that CD147 mediates TGF-β1-induced EMT and tumorigenicity in HNSCC. Hence, CD147 may serve as a vital therapeutic target in HNSCC.

摘要

上皮-间质转化(EMT)是一个生理过程,在此过程中上皮细胞获得间质细胞的运动和侵袭特性,导致细胞迁移和侵袭行为增加,这是癌症进展的重要机制。因此,控制EMT用于癌症治疗,包括头颈部鳞状细胞癌(HNSCC),势在必行。在与EMT相关的因素中,转化生长因子-β(TGF-β)是一种公认的强效诱导剂。最近的研究表明,免疫球蛋白超家族成员CD147促进EMT。然而,CD147在HNSCC的EMT及随后的肿瘤发生中的作用尚未完全阐明。本研究旨在探讨CD147在HNSCC的EMT及相关肿瘤发生中的作用。本研究使用了两种HNSCC细胞系SAS和FaDu进行研究。在HNSCC细胞中,TGF-β1诱导细胞呈纺锤形形态变化,蛋白质印迹分析显示TGF-β1诱导EMT标志物发生变化,波形蛋白下调,E-钙黏蛋白上调,但CD147增加。此外,TGF-β1增加了HNSCC细胞的迁移。然而,在SAS细胞中,通过小干扰RNA(siRNA)使CD147沉默后,TGF-β1诱导的EMT标志物改变减弱。此外,CD147沉默后,TGF-β1诱导的SAS细胞侵袭减弱。总之,本研究表明CD147介导TGF-β1诱导的HNSCC的EMT和肿瘤发生。因此,CD147可能是HNSCC的一个重要治疗靶点。

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