摘要
目的探索趋化因子受体CXCR4和VEGF-C与乳腺癌淋巴转移的关系,为研究干预乳腺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45例原发性乳腺癌组织中趋化因子受体CXCR4mRNA的表达及VEGF-CmRNA的表达,探索其与乳腺癌腋淋巴结转移的关系;Boyden趋化小室法检测CX-CR4不同表达状态乳腺癌细胞的趋化活性和趋化抑制性。结果45例原发性乳腺癌组织均有不同程度的CXCR4mRNA和VEGF-CmRNA的表达。37例CXCR4mRNA呈高表达,表达率为82.22%,73.33%的VEGF-CmRNA高表达(33/45);VEGF-CmRNA高表达组的CXCR4mRNA的高表达率大(P<0.05);CX-CR4mRNA的表达与乳腺癌腋淋巴结转移呈正相关(P<0.05);CXCR4的配体SDF-1对乳腺癌细胞的平均趋化率为75%,经抗CXCR4单克隆抗体处理后癌细胞的平均趋化率下降至34%,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)。结论原发性乳腺癌CXCR4的表达和VEGF-C的表达与肿瘤腋淋巴结转移呈正相关;CXCR4的功能状态影响乳腺癌细胞的迁移活性。由此提示,通过干预趋化因子受体CXCR4和VEGF-C的活性可能成为阻断乳腺癌淋巴转移的新靶点。
Objective: To explore the role of ehemokine receptor CXCR4 on lymphatic metastasis induced by VEGF- C in breast carcinoma and make it possible to offer a new theory and method on metastasis intervention. Methods:Tbe expression of CXCR4 and VEGF - C mRNA were determined by reverse transcription PCR ( RT - PCR) in cases of 45 primary breast carcinomas, and the migration and inhibition response of CXCR4 to ehemokine stromal derived factor - 1 (SDF - 1 or CXCL12) were detected by Boyden chemotaxis assay. Results:All of 45 cases with primary breast carcinomas had been detected different expression levels of CXCR4 and VEGF - C mRNA, in which 37 cases presented high expression levels of CXCR4, and the rate was 82.22% (37/45). The group with higher expression of VEGF- C mRNA presented higher expression of CXCR4 mRNA(P 〈0.05 ), and the expression of CXCR4 mRNA was positively correlated with axiUary lymph node metastasis in primary breast eareinomas(P 〈0.05 ). The average ehemotaxis activity of CXCR4 to SDF - 1 could be evaluated as 75% in breast cancer cells, but it dropped to 34% after using anti- CXCR4 monoclonal antibody, and the difference was significant( P 〈0.05 ). Conclusion:There was a positive correlation between axillary lymphatic metastasis and the expression of CXCR4 and VEGF - C mRNA in primary carcinomas. The functional status of CXCR4 could effect the chemotaxis of breast cancer cells, it may be a new target aiming to blocking lymphatic metastasis by interfering with the activity of CXCR4 and VEGF - C.
出处
《现代肿瘤医学》
CAS
2006年第5期543-546,共4页
Journal of Modern Oncology
基金
湖南省社会发展科技项目资助(No.OISSY2008-41)