Recognize the role of CD146/MCAM in the osteosarcoma progression: an in vitro study

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: MG63 was transfected with lentivirus to express CD146 ectopically, and anti-CD146 neutralizing antibody ab75769 was used to inhibit 143B. Cyclic migration of MG63 and co-culture between MG63 and 143B were used to explore the role of OS malignancy in CD146 expression. The effect of OS cell medium (CM) on endothelium behaviors was assessed, and the expression changes of CD146 before and after co-culture of endothelium and OS were evaluated. Finally, the expression of CD146 in OS was detected 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.