Background: Osteosarcoma (OS) is a common malignant bone tumor with poor prognosis. We previously reviewed that CD146 is correlated with multiple cancer progression, while its impact on OS is currently not systematically studied. Methods: we transfected MG63 with lentivirus to express CD146 ectopically, combining with anti-CD146 neutralizing antibody ab75769 to inhibit 143B, to observe the intrinsic relationship between CD146 and OS. In addition, we used Transwell co-culture system and

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... gned cyclic migration assay to explore the effect of CD146 on the interaction between OS and endothelium. Finally, we also detected the expression of CD146 in OS under different culture conditions, including hyperoxia, low oxygen, high glucose and low glucose conditions.Results: CD146 promoted the colony formation, migration, invasion and homotypic adhesion of OS cells, and reducing the concentration of soluble CD146 in the OS medium inhibited the proliferation, migration and lumen formation of the cultured endothelium. However, CD146 did not affect the adhesion between OS and endothelium, nor did co-culture of both sides affect the CD146 expression. Similarly, the proliferation, migration and CD146 expression of MG63 remained unchanged after many cycles of migration itself, as did its co-culture with 143B for expressing CD146. In addition, we also showed that high glucose promoted the expression of CD146 in OS, while hypoxia had the opposite effect. Conclusions: These findings demonstrate that CD146 promotes OS progression by mediating pro-tumoral and angiogenic effects. Thus, CD146 could be a potential therapeutic target for OS, especially for OS patients with diabetes.