自身抗体在肿瘤的致癌或者抑癌机制中发挥着重要调控作用。然而，自身抗体对骨肉瘤的影响及作用机制尚未明确。我们课题组前期获取了全人源单克隆自身抗体1G3。课题组前期研究结果表明，1G3可以特异性结合的靶蛋白为DDX5；DDX5的表达与β-catenin的表达呈正相关，DDX5减少会抑制β-catenin在细胞核内的聚集，从而抑制β-catenin/TCF信号通路，进而促进细胞凋亡；同时，本课题研究发现1G3可以抑制骨肉瘤细胞的活性，上调骨肉瘤细胞内活化的caspase-3表达水平。此外，我们前期构建了1G3复合透明质酸水凝胶系统，在3D微环境中可以抑制骨肉瘤细胞U2OS细胞团的生长。本课题从分子和细胞水平、体内小鼠模型等多层次、多角度验证自身抗体1G3对骨肉瘤的影响，阐明1G3的抑癌机制；为骨肉瘤的发病机制提供可靠的实验数据，为骨肉瘤的特异性诊断和靶向治疗提供新的研究方向。

Autoantibodies play an important role in the carcinogenesis or tumor suppressive mechanism. The effect of autoantibodies on osteosarcoma is not yet clear. In previous work, we prepare the monoclonal antibody 1G3 from the whole human source. It could bind to DDX5 specifically. The expression of DDX5 is positively correlated with beta-catenin. The downregulation of DDX5 could inhibit the accumulation of beta-catenin, block the beta-catenin /TCF signaling pathway in the nucleus, and induce cells apoptosis. This study found that 1G3 could inhibit cell activity and promote caspase-3 expression in osteosarcoma cells. In addition, we constructed composite hydrogel system of 1G3 and hyaluronic acid. This system can inhibit the growth of U2OS cell spheroids in 3D microenvironment. In this study, the effect of 1G3 on osteosarcoma was verified on molecular, cell level and the mouse model. It provides reliable experimental data for the pathogenesis and new research direction for the specific diagnosis and targeted therapy of osteosarcoma.