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[CXC亚家族受体4调控口腔鳞状细胞癌上皮-间质转化影响体外淋巴转移的实验研究]

[The experimental study of CXC subfamily receptor 4 modulating oral squamous cell carcinoma epithelial-mesenchymal transition to influence lymphatic metastasis in vitro].

作者信息

Zhang Shu, Wang Bo, Zhou Xuan, Yue Kai, Wang Xudong

机构信息

Department of Maxillofacial and E.N. T (ear, nose and throat) Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Reaserch Center for Cancer & Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin 300060, China.

Department of Maxillofacial and E.N. T (ear, nose and throat) Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Reaserch Center for Cancer & Key Laboratory of Cancer Prevention and Therapy Tianjin, Tianjin 300060, China. Email:

出版信息

Zhonghua Kou Qiang Yi Xue Za Zhi. 2014 Mar;49(3):171-6.

Abstract

OBJECTIVE

To sutdy the effect and mechanism of CXC chemokine receptor 4 (CXCR-4 )modulating oral squanmous cell carcinoma (OSCC) epithelial-mesenchymal transition (EMT)to mediate tumor lymphatic metastasis.

METHODS

Immunohistochemistry was used to detect the CXCR-4 and EMT related proteins among 60 OSCC samples with different lymph node metastasis status and the relationship with clinicopathological features and EMT related factors were analyzed. The small interfering RNA (siRNA) was applied to silence CXCR-4 in Tscca cell.Reverse transcription-PCR and Western blotting were used to observe the inhibitory effect. The wound healing assay, transwell invasion assay and flow cotometry were used to detect Tscca cell migration, invasion ability and apoptosis.

RESULTS

In lymph node metastasis group, the expression of CXCR-4, N-cadherin, Twist, Snail were higher than those in non-lymph node metastasis group. CXCR-4 showed a positive correlation with Twist, Snail, N-cadherin (correlation coefficient:0.300, 0.256, 0.333, P < 0.05), but negatively correlated with β-catenin (correlation coefficient:-0.497, P < 0.05). CXCR-4 silencing inhibited the migration and invasion of Tscca cell and induced apoptosis of the cell. Western blotting results indicated that N-cadherin, matrix metalloproteina-2/9 (MMP-2/9) was decreased (N-cadherin: F = 20.999, P = 0.002; MMP-2: F = 47.156, P = 0.000; MMP-9: F = 142.317, P = 0.000) while E-cadherin was up-regulated (F = 111.022, P = 0.000).

CONCLUSIONS

CXCR-4 might play a critical role in the metastasis of OSCC via modulating EMT.

摘要

目的

研究CXC趋化因子受体4(CXCR-4)调控口腔鳞状细胞癌(OSCC)上皮-间质转化(EMT)介导肿瘤淋巴转移的作用及机制。

方法

采用免疫组织化学法检测60例不同淋巴结转移状态的OSCC标本中CXCR-4及EMT相关蛋白,分析其与临床病理特征及EMT相关因子的关系。应用小干扰RNA(siRNA)沉默Tscca细胞中的CXCR-4。采用逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹法观察抑制效果。采用伤口愈合实验、Transwell侵袭实验和流式细胞术检测Tscca细胞的迁移、侵袭能力及凋亡情况。

结果

淋巴结转移组中CXCR-4、N-钙黏蛋白、Twist、Snail的表达高于无淋巴结转移组。CXCR-4与Twist、Snail、N-钙黏蛋白呈正相关(相关系数分别为0.300、0.256、0.333,P<0.05),与β-连环蛋白呈负相关(相关系数为-0.497,P<0.05)。CXCR-4沉默抑制了Tscca细胞的迁移和侵袭,并诱导细胞凋亡。蛋白质免疫印迹结果显示,N-钙黏蛋白、基质金属蛋白酶-2/9(MMP-2/9)表达降低(N-钙黏蛋白:F=20.999,P=0.002;MMP-2:F=47.156,P=0.000;MMP-9:F=142.317,P=0.000),而E-钙黏蛋白表达上调(F=111.022,P=0.000)。

结论

CXCR-4可能通过调控EMT在OSCC转移中起关键作用。

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