摘要
目的探讨趋化因子受体CXCR4异质性在人肺癌(Human Lung Cancer,简称HLC)转移机制中的作用。方法以免疫组织化学方法检测HLC组织中CXCR4蛋白表达水的表达;通过原代培养HLC细胞,进行流式细胞仪分选出CXCR4+HLC细胞和CXCR4-HLC细胞两个亚群。利用Transwell小室法,检测两个亚群细胞的体外侵袭力;检侧CX-CL12和CXCR4的拮抗剂AMD 3100对CXCR4+HLC细胞和CXCR4-HLC细胞体外侵袭能力的影响。结果免疫组化检查提示肺癌组织中CXCR4阳性表达51例,阳性表达率为60.7%;经流式细胞仪检查CXCR4阳性表达率为89.4%;Transwell侵袭实验结果显示,CXCR4+HLC细胞穿过基底膜的细胞数为(34.07±7.05)个,CXCR4-HLC细胞仅为(17.60±4.01)个。CXCR4+HLC细胞体外侵袭能力明显强于CXCR4-HLC细胞(P<0.05,差异有统计学意义);CX-CR4+HLC细胞株+CXCL12(30 ng/ml)穿过基底膜的细胞数为(67.60±3.87)个,显著低于CXCR4+HLC细胞株+CX-CL12 100 ng/ml组,其穿膜细胞数为(106.1±24.2)个(P<0.05,差异有统计学意义);CXCL12(100 ng/ml)+AMD3100组仅为(24.53±5.50)。AMD3100组与另两组比较有统计学意义(P<0.05)。结论人肺癌组织中CXCR4表达存在异质性;趋化因子CXCL12可促进CXCR4表达阳性的肺癌细胞侵袭活性,而CXCR4的抑制剂AMD3100能抑制这种侵袭活性。
Objective To explore the heterogeneity of chemokine receptor 4（CXCR4） and its role in the directional migration of human lung cancer（HLC）.Methods CXCR4 protein in lung cancer tissues was detected by immunohistochemistry;HLC cells from a patient with HLC were cultured in vitro by primary tissue culture technique.Flow cytometry was used to isolate CXCR4^＋HLC cells and CXCR4^＋ HLC cells.The difference of invasiveness between two subpopulations was measured by Transwell experiment.The influence of exogenous chemokine CXCL12 and AMD3100（specific antagonist of CXCR4） on the invasive ability was observed.Results The positive rate of CXCR4 protein in HLC cells was 60.7% by immunohistochemistry,and 89.4% by flow cytometry.In Transwell experiment,the cell number that infiltrated transwell membrane in CXCR4^＋ group（34.07 ± 7.05） was higher than that in CXCR4^-group（17.60 ± 4.01）.The exogenous chemokine CXCL12 greatly promoted the invasion of CXCR4^＋ cells,and the quantity of the trans-membrane cells was the most under 100 ng / ml CXCL12.AMD3100 greatly inhibited the invasive ability of CXCR4^＋ cells.The differences between the two groups were statistically significant（P〈0.05）.Conclusion The expression of CXCR4 in lung cancer is heterogeneous with respect to characteristics on invasion and metastasis potentiality.CXCL12-CXCR4 axis may play an important role in lung cancer cells proliferation and migration,and AMD3100 which is CXCR4 blocker can efficiently decrease this effect.
出处
《中华全科医学》
2013年第8期1169-1170,1193,F0003,共4页
Chinese Journal of General Practice
基金
湖北省自然科学基金资助项目(201006809
2011CHB018)
关键词
肺癌
异质性
趋化因子受体4
转移
侵袭
Lung cancer
Heterogeneity
Chemokine receptor CXCR4
Metastasis
Invasion
