骨肉瘤的高转移特性是当前限制患者生存率进一步提高的关键因素，抑制肿瘤相关巨噬细胞（TAM）M2型极化的抗转移策略受到广泛关注，但在骨肉瘤中相关研究尚处于起步阶段。我们前期发现，全反式维甲酸（ATRA）可特异性地抑制TAM M2型极化，并发挥极为显著的抗骨肉瘤转移作用，同时伴随着细胞内neddylation修饰水平的提高。基于此，本课题将进一步明确M2型极化与骨肉瘤转移的相关性；研究ATRA通过抑制M2型极化发挥抗骨肉瘤转移作用的可能机制；探索ATRA激活neddylation的分子机制及其在抑制M2型极化中的作用，及对RARα及其下游靶基因的分子调控机制。通过本课题的研究，不仅将阐明ATRA调控M2型极化从而发挥抗骨肉瘤转移作用的新分子机制，探索通过干预M2型极化治疗肿瘤转移的可行性，并为设计和发现基于M2型极化调控的全新抗肿瘤转移药物提供潜在靶点和理论依据。

High rate of metastasis is a characteristic of osteosarcoma, which limited patient survival. Though the anti-metastasis strategy by inhibition of tumor-associated macrophages (TAM) M2 type polarization has gained wide attention, its relation with osteosarcoma metastasis remains elusive. Our study found that all-trans retinoic acid (ATRA) could specifically inhibit TAM M2 type polarization, and display significant anti-metastasis efficacy in osteosarcoma, which is accompanied by an increased level of intracellular neddylation. We wish to further clarify the relation between M2 type polarization with osteosarcoma metastasis, reveal the possible mechanisms underlying the anti-metastasis potential of ATRA by inhibition of M2 type polarization, explain how ATRA-activated neddylation suppressed M2 type polarization, and find the downstream targets of RARα after its neddylation. Our study not only will clarify how ATRA regulates M2 type polarization during osteosarcoma metastasis, but also test the feasibility of anti-metastasis treatment via M2 type polarization intervention, thus providing the potential target and theoretical basis for the design and discovery of novel anti-tumor drugs.