摘要
目的:探讨趋化因子CXCL12/CXC趋化因子受体4(CXC chemokine receptor4,CXCR4)作用轴在乳腺癌骨转移中的功能角色。方法:以含不同浓度梯度的CXCL12培养液培养乳腺癌MDA-MB-231细胞后,应用免疫细胞化学法检测MDA-MB-231细胞中CXCR4的表达,Transwell双室培养体系检测MDA-MB-231细胞的迁移能力。向裸鼠左心室注射MDA-MB-231细胞悬液或100nmol/L CXCL12和乳腺癌MDA-MB-231细胞,建立乳腺癌骨转移模型,通过病理学检查分析骨转移情况,蛋白质印迹法检测骨转移灶组织中CXCL12的表达。结果:MDA-MB-231细胞中CXCR4的表达水平与CXCL12具有明显的剂量相关性(r=0.92,P<0.05);MDA-MB-231细胞的迁移百分率随着CXCL12浓度的增加而上升。与单纯乳腺癌MDA-MB-231细胞裸鼠移植瘤模型组比较,加入CXCL12的乳腺癌MDA-MB-231细胞裸鼠移植瘤模型组中,胸骨和椎骨的转移灶数量增加最为明显(P<0.01);并且,胸骨和椎骨转移灶组织中CXCL12蛋白呈高表达。结论:乳腺癌骨转移与CXCL12/CXCR4作用轴的关系密切,可能成为具有较大科研价值的基因治疗靶点。
Objective： To investigate the functional role of CXCL12/CXCR4 （chemokine receptor 4） in bone metastatic breast cancer cells. Methods： After the breast cancer MDA-MB-231 cells were cultured in medium containing different concentrations of CXCL12, the expression of CXCR4 in MDA-MB-231 cells was detected by immunocytochemistry and the migration ability of MDA-MB-231 cells was detected by Transwell double chamber culture system. The MDA-MB-231 cells or MDA-MB-231 cells plus 100 nmol/L CXCL12 were injected into left ventricle of nude mice to establish the model of bone metastasis from breast cancer cells. The condition of bone metastasis was analyzed by pathological examination, and then the expression level of CXCL12 in metastatic bone lesions was detected by Western blotting. Results： The expression level of CXCR4 in MDA-MB-231 cells was significantly associated with CXCL12 in dose-related manner （r = 0.92, P 〈 0.05）. The percentage of migratory MDA-MB-231 cells was gradually increased with the increasing concentration of CXCL12. As compared with MDA-MB-231 xenograft model in nude mice, the numbers of metastatic lesions in the vertebrae and sternum were much more in MDA-MB-231 xenograft model in nude mice treated with CXCL12 （P 〈 0.01）, meanwhile the expression levels of CXCL12 protein were also higher in metastatic lesions in vertebrae and sternum. Conclusion： The CXCL12/ CXCR4 role-axis is closely related to bone metastasis from breast cancer cells, which may become a target of gene therapy.
出处
《肿瘤》
CAS
CSCD
北大核心
2013年第6期497-501,共5页
Tumor
基金
天津市滨海新区卫生局医药卫生科技项目(编号:2011BHKY019)
