华西口腔医学杂志

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趋化因子受体CXCR4及其配体CXCL12在口腔鳞状细胞癌细胞增殖和迁移中的作用

尹东 张佐 高素 李斌   

  1. 宁夏回族自治区人民医院 口腔科, 银川 750021
  • 出版日期:2013-02-01 发布日期:2013-02-01
  • 通讯作者: 尹东,Tel:13995283853

The role of chemokine receptor CXCR4 and its ligand CXCL12 in the process of proliferation and migration of oral squamous cell carcinoma

Yin Dong, Zhang Zuo, Gao Su, Li Bin.   

  1. Dept. of Stomatology, The People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750021, China
  • Online:2013-02-01 Published:2013-02-01

摘要:

目的  检测趋化因子受体CXCR4及其配体CXCL12在口腔鳞状细胞癌细胞中的表达及其在肿瘤细胞增殖和 迁移中的作用。方法  采用逆转录聚合酶链式反应和Western blot法检测20例口腔鳞状细胞癌组织、颈部淋巴结组织、舌鳞状细胞癌细胞株Tca8113、颊鳞状细胞癌细胞株Bca885和10例正常口腔黏膜组织中CXCR4的表达,采用逆转录聚合酶链式反应检测CXCL12的表达,通过MTT法检测细胞的增殖能力,通过趋化实验观察CXCR4特异性配体CXCL12对口腔鳞状细胞癌细胞的趋化迁移作用。结果  1)在口腔鳞状细胞癌组织、Tca8113细胞及Bca885细胞中, CXCR4 mRNA的相对表达量分别为2.31±1.13、1.89±1.20、1.67±1.10,CXCR4蛋白的相对表达量分别为1.36±0.15、1.85±0.34、1.97±0.23,正常口腔黏膜组织在mRNA及蛋白质水平均未检测到CXCR4表达。口腔癌患者颈部淋巴结组 织中,CXCL12 mRNA表达量的平均值为1.14±0.87,而口腔鳞状细胞癌组织和正常口腔黏膜组织未检测出CXCL12的 表达。2)口腔鳞状细胞癌细胞在CXCL12作用下增殖反应明显增强,CXCR4抗体可明显抑制肿瘤细胞的增殖。3)趋化实验显示CXCL12可诱导口腔鳞状细胞癌细胞发生明显迁移,在30~100 ng·mL-1的范围内,诱导口腔鳞状细胞癌细 胞迁移的作用呈明显量效关系。结论  CXCR4/CXCL12受体配体系统可介导口腔鳞状细胞癌细胞的增殖和迁移, 在癌细胞向颈部淋巴结转移中发挥着重要作用。

关键词: 口腔鳞状细胞癌, 趋化因子受体, 增殖, 迁移

Abstract:

Objective  To investigate the expression of chemokine receptor CXCR4 and its ligand CXCL12 in oral squamous cell carcinoma(OSCC) cells, and their effects on proliferation and migration of tumor cells. Methods  The expression of CXCR4 mRNA and protein in 20 cases of OSCC tissue, cervical lymph nodes, tongue cancer cell line Tca8113, buccal cancer cell line Bca885, and 10 specimens of normal oral mucosa tissue were examined by reverse transcriptase-polymerase chain reaction(RT-PCR) and Western blot. The expression of CXCL12 mRNA was examined by RT-PCR. MTT assay was used to evaluate the CXCR4/CXCL12 influence on proliferation of tumor cells. Chemotaxis and migration response to CXCR4 particular ligand-CXCL12 were detected by chemotaxis assay. Results  1)Ex- pression levels of CXCR4 mRNA and protein in OSCC tissues, Tca8113 and Bca885 cells were 2.31±1.13, 1.89±1.20,1.67±1.10 and 1.36±0.15, 1.85±0.34, 1.97±0.23, respectively. CXCR4 mRNA and protein couldn’t be detected in normal tissues. CXCL12 mRNA level in cervical lymph nodes was 1.14±0.87, CXCL12 mRNA couldn’t be detected in OSCC and normal tissues. 2)In MTT assay, recombinant CXCL12 stimulated proliferation of tumor cells and CXCR4 neutra- lization by monoclonal antibodies decreased proliferation. 3)The chemotactic migration of OSCC cells could be induced by CXCL12. CXCL12 at a concentration between 30 ng·mL-1 and 100 ng·mL-1 induced the chemotactic migration of OSCC cells in a dose-dependent manner. Conclusion  CXCR4/CXCL12 system may promote proliferation and migration of tumor cells, and may play an important role in lymph node metastasis of OSCC.

Key words: oral squamous cell carcinoma, chemokine receptor, proliferation, migration