CXCR4 promotes metastases to the lung of osteosarcoma xenografts in mice

Objectives: To investigate the effect of CXCR4 on the metastasis of osteosarcoma cells. Methods: The in vitro invasion and migration of osteosarcoma MG-63 cells was assessed by transwell assay. Bioluminescence was applied to evaluate the metastasis of osteosarcoma cells in a mouse xenograft model. Changes in the expression of the metastasis-related cytokines vascular endothelial growth factor (VEGF), matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed by western blotting. Results: A significantly (p<0.05) higher invasion ability was observed in MG-63 cells with CXCR4 overexpression by transwell assay. A similar size of orthotopic osteosarcoma but more pulmonary tumors were found in mice injected with CXCR4-overexpressing MG63 cells than the control. Moreover, the expressions of VEGF and MMP-9 in the groups with CXCR4 overexpression were significantly (p<0.05) higher than those in the control; however, the opposite results were found for TIMP-1 in cultured MG-63 cells and in mouse orthotopic osteosarcoma and pulmonary tumors. Conclusions: CXCR4 up-regulates the expression of VEGF and MMP-9 but down-regulates TIMP-1, thereby promoting lung metastases of human osteosarcoma cells. Our findings suggest that CXCR4 is a potential target for the treatment of human osteosarcoma.