趋化因子受体CCR7对口腔鳞癌细胞增殖和迁移的影响

Effects of chemokine receptor CCR7 on proliferation and migration of oral squamous cell carcinoma

目的检测趋化因子受体CCR7[Chemokine(C-C)Receptor 7]的表达及其对口腔鳞癌细胞增殖和迁移的影响。方法采用反转录聚合酶链反应(RT-PCR)和Western Blot检测20例口腔鳞癌组织、口腔鳞癌细胞系Tca-8113、腺样囊性癌细胞系ACC-M(Adenoid Cystic Carcinoma,ACC-M)和10例正常口腔黏膜组织中CCR7的表达。用MTT法检测细胞的增殖能力,通过趋化实验观察在CCR7的配体次级淋巴组织趋化因子(Sec-ondary Lymphoid-tissue Chemokine,SLC)作用下对口腔鳞癌细胞的趋化迁移作用。结果①在口腔鳞癌组织和Tca-8113细胞中,CCR7在mRNA及蛋白水平均有强的表达,ACC-M细胞系中CCR7弱表达,而在正常口腔黏膜组织细胞不表达。②口腔鳞癌细胞在SLC作用下增殖反应明显增强,CCR7抗体可明显抑制肿瘤细胞的增殖。③体外实验显示SLC可诱导口腔鳞癌细胞发生明显迁移,在30、50 ng/ml的实验浓度范围内,诱导口腔鳞癌细胞迁移的作用呈明显量效关系。结论 CCR7/SLC受体配体系统可通过介导口腔鳞癌细胞的增殖、侵袭和迁移,从而在口腔鳞细胞向颈部淋巴结转移中发挥着重要作用,CCR7有可能成为口腔鳞癌治疗的新靶点。

Objective To investigate the expression of chemokine（C-C）receptor 7 in oral squamous cell carcinoma（OSCC）cells and its effects on proliferation and migration of tumor cells.Methods The expression of CCR7 mRNA and protein in 20 cases of OSCC tissue,tongue cancer cell line Tca-8113,adenoid cystic carcinoma cell line ACC-M,and 10 specimens of normal oral mucosa tissue were examined by reverse transcriptase-polymerase chain reaction（RT-PCR）and western blot.MTT assay was used to evaluate the CCR7/ SLC influence on proliferation of tumor cells.Chemotaxis and migration response to CCR7 ligand-SLC was detected by chemotaxis assay.Results There was strong expression of CCR7 mRNA and protein in oral cancer tissues and Tca-8113 cells,and the weak expression of CCR7 mRNA and protein in ACC-M cells,and could not be detected in normal oral mucosa tissue.In MTT assay,recombinant SLC stimulated proliferation of tumor cells and CCR7 neutralization by monoclonal antibodies decreased proliferation.The chemotactic migration of OSCC cells could be induced by SLC.SLC at a concentration between 30 ng/ml and 50 ng/ml induced the chemotactic migration of OSCC cells in a dose-dependent manner.Conclusion CCR7/ SLC system may promote proliferation and invasion and migration of tumor cells,and may play an important role in cervical lymph node metastasis of OSCC.CCR7 as a potential therapeutic target in advanced cases of OSCC.