CXCR4 promotes metastases to the lung of osteosarcoma xenografts in mice

被引:0
作者
Chen, Shunyou [1 ,2 ]
Zhang, Tao [2 ]
Pan, Yuancheng [2 ]
Lin, Ran [2 ]
Chen, Dongdong [2 ]
Weng, Yan [2 ]
Yu, Bin [1 ]
Zhang, Yiyuan [2 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Orthoped & Traumatol, 1813 North Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China
[2] Xiamen Univ, Fuzhou Hosp 2, Dept Orthoped, Fuzhou, Fujian, Peoples R China
关键词
CXCR4; osteosarcoma; pulmonary metastasis; VEGF; TIMP-1; MESENCHYMAL STEM-CELLS; BREAST-CANCER; UP-REGULATION; PATHWAYS; PHENOTYPE; CARCINOMA; CYTOKINES; INVASION; PROGRESS; BIOLOGY;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:9441 / 9447
页数:7
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