骨肉瘤转移是骨肉瘤治疗失败的主要原因。间充质样运动和阿米巴样运动是肿瘤细胞运动的两种基本形式，它们协同作用促进了肿瘤转移。然而这两种运动的调控机制仍不清楚。申请者前期的研究发现βig-h3分别与介导细胞间充质样运动关键分子integrin α2β1和介导阿米巴样运动关键分子AnnexinII相互作用促进骨肉瘤转移。进一步研究发现上调βig-h3表达细胞呈现间充质样运动特点，下调βig-h3表达细胞呈现阿米巴样运动特点。但是βig-h3能否调控细胞运动从而促进骨肉瘤的转移，目前尚未报道。本项目拟从βig-h3调控骨肉瘤细胞运动入手，应用βig-h3基因敲除小鼠和细胞等模型，采用小动物活体成像、细胞3D培养、活细胞工作站等手段，原位、实时、动态研究骨肉瘤转移过程中βig-h3对细胞运动的调控，明确βig-h3调控骨肉瘤细胞运动促进骨肉瘤转移的分子机制，为骨肉瘤转移的临床诊治提供新的线索和靶点。

Osteosarcoma metastasis is the main reason for the failure of osteosarcoma treatment. Mesenchymal mode movement and amoeboid mode movement is the two basic forms of tumor cell movement, and the two movement modes interconvert to promote tumor metastasis. However, the regulatory mechanism of cell motion is still unclear. Our previous studies has found that βig-h3 interacts with integrin α2β1 and AnnexinII, which are involved in the regulation of mesenchymal mode movement and amoeboid mode movement, respectively. Moreover, osteosarcoma cells appears amoeboid mode movement when upregulation βig-h3 expression and osteosarcoma cells appears mesenchymal mode movement when downregulation βig-h3 expression. However, it has not been reported that whether βig-h3 may regulate cell movement modes and promotes osteosarcoma metastasis. In this study, we use gene knockout mice、gene knockout cell lines, small animal imaging, live cell workstation and the 3D cell culture system to monitor the modes of cell movement and explore the role of βig-h3 in the regulation of cell movement, and clarify the mechanism of osteosarcoma metastasis.Thus giving rise to the promise of new clue to inhibit metastasis in osteosarcoma treatments.