Survivin and vascular endothelial growth factor are associated with spontaneous pulmonary metastasis of osteosarcoma: Development of an orthotopic mouse model

The high rate of pulmonary metastases of osteosarcoma (OS) presents a therapeutic challenge in the field of orthopedics. Therefore, there is a marked requirement to establish a spontaneous pulmonary metastasis animal model of OS, within which potential antitumor agents may be evaluated for their ability to inhibit the growth and pulmonary metastasis of OS, as well as to identify potentially associated biomarkers of OS metastasis. In the present study, rodent OS cells (UMR106-01) were injected into the right tibia of athymic nude mice. The mice were sacrificed weekly by cervical dislocation at one to five weeks following inoculation. The orthotopic mice developed tumor masses in the right tibia one week following inoculation. At three weeks, multiple nodules were observed in the lungs. The expression of survivin and vascular endothelial growth factor (VEGF) was analyzed in the tumors and lungs via immunohistochemistry. The positive expression of survivin and VEGF was identified in the local tumor and lung tissue of the orthotopic mice, however was not observed in the tissues of the healthy control mice. The orthotopic model established in the current study presents a valuable tool for the investigation of factors that promote or inhibit OS growth and/or metastasis. In addition, it was identified that survivin and VEGF may be significant in the lung metastasis of OS.