Hypoxia-regulated exosomes mediate M2 macrophage polarization and promote metastasis in chondrosarcoma

Chondrosarcoma is a primary malignant bone tumor. Traditional therapy is not very effective, and it is prone to metastasis in the late stage. The tumor microenvironment (TME) plays a key role in the progression and metastasis of chondrosarcoma, and hypoxia is one of the key factors in the formation of TME. However, the detailed mechanism of how hypoxia affects tumor progression and metastasis in chondrosarcoma is still not fully understood. In this study, we focused on the mechanism of interaction between hypoxic chondrosarcoma cells (SW1353) and macrophages. Our results suggest that hypoxia enhances the release of exosomes from chondrosarcoma cells. These hypoxia-induced exosomes promoted macrophage polarization towards the M2 phenotype, characterized by the expression of CD163 and CD206, but not the M1 phenotype, characterized by CD86 expression. Further analysis revealed that M2 macrophages polarized by exosomes expressed arginase-1 and feedback to chondrosarcoma cells to promote migration. These results suggest that chondrosarcoma cells secrete more exosomes in a hypoxic microenvironment, and these hypoxia-derived exosomes induce the polarization of macrophages into an M2 phenotype, ultimately promoting the metastatic behavior of chondrosarcoma cells.