CXCR4在VEGF-C介导的胃癌淋巴道转移中的作用

Role of CXCR4 in lymph node metastasis promoted by VEGF-C in gastric carcinoma

目的探索趋化因子受体CXCR4和VEGF-C与胃癌淋巴道转移的关系,为研究干预胃癌淋巴转移的新方法提供理论依据。方法采用RT-PCR方法检测86例胃癌组织中趋化因子受体CXCR4 mRNA的表达及VEGF-C mRNA的表达,探索其与胃癌淋巴结转移的关系;Boyden趋化小室法检测CXCR4不同表达状态胃癌细胞的趋化活性和趋化抑制性。结果86例胃癌组织均有不同程度的CXCR4 mRNA和VEGF-C mRNA的表达。53例CXCR4 mRNA呈高表达,表达率为61.63%,VEGF-C mRNA高表达率为56.98%(49/86);VEGF-C mRNA高表达组中的CXCR4 mRNA的表达率也较高;CXCR4 mRNA的表达与胃癌淋巴结转移呈正相关(P<0.05);CXCR4的配体SDF-l对胃癌细胞的平均趋化率为81%,经抗CXCR4单克隆抗体处理后癌细胞的平均趋化率下降至30%,CXCR4被特异性抗体封闭前后的癌细胞趋化活性有显著性差异(P<0.05)。结论胃癌CXCR4的表达和VEGF-C的表达与胃癌淋巴结转移呈正相关;CXCR4的功能状态影响胃癌细胞的迁移活性。通过干预趋化因子受体CXCR4和VEGF-C的活性可能成为阻断胃癌淋巴转移的新靶点。

Objective To explore the role of chemokine receptor CXCR4 in lymphatic metastasis induced by VEGF-C in gastric carcinoma. Methods The mRNA expressions of CXCR4 and VEGF-C were determined by reverse transcription PCR （RT-PCR） in 86 cases of primary breast carcinoma, and the migration and inhibition response of CXCR4 to chemokine stromal derived factor-1 （SDF-1 or CXCL12） were detected by Boyden chemotaxis assay. Resaults Out of 86 cases, 53 cases presented high expression levels of CXCR4 （61.63%, 53/86）, 49 cases showed high expression levels of VEGF-C mRNA （56.98%, 49/86）. The cases with higher expression of VEGF-C mRNA presented higher expression of CXCR4 mRNA. The expression of CXCR4 mRNA was positively correlated with lymph node metastasis in primary gastric carcinoma （P 〈 0. 05 ）. The average chemotaxis activity of CXCR4 to SDF-1 was evaluated as 81% in gastric cancer cells, but dropped to 30% after using anti-CXCR4 monoclonal antibody, with significant difference （P 〈 0. 05）. Conclusion There is a positive correlation between lymphatic metastasis and the expression of CXCR4 and VEGF-C mRNA in primary gastric carcinoma. The functional status of CXCR4 affects the chemotaxis of gastric cancer cells.