Upregulation of Mad2 facilitates in vivo and in vitro osteosarcoma progression.

It has been reported that overexpression of Mad2 in transgenic mice leads to a wide variety of tumors, and Mad2 overexpression causes lung tumor relapse after oncogene withdrawal. In a previous study we demonstrated that Mad2 is abnormally upregulated in human osteosarcoma, however, the underlying mechanisms remain unknown. In this study, we found that transient Mad2 overexpression is sufficient to cause early dyscrasia and decreased survival in a xenotransplantation osteosarcoma mouse model, and Mad2 overexpression is associated with increased invasiveness and pulmonary metastasis. We also found that upregulation of Mad2 was accompanied by enhanced capability to self-renew. Our data validate the correlation between upregulation of Mad2 and osteosarcoma advancement, and that the underlying mechanisms involve the increase of invasiveness and cancer stem cell properties.