Heterogeneity of Chemokine Receptor CXCR4 and Its Relationship with Invasion and Metastasis of Human Lung Cancer Cells

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.