Tumor-derived Exosomes Induced M2 Macrophage Polarization and Promoted the Metastasis of Osteosarcoma Cells Through Tim-3

Osteosarcoma, the most prevalent primary malignancy of bone, is often presented with high-grade subclinical metastatic disease that metastasizes at very early stages. Exosomes, as molecular information carriers, may play a potent role in occurrence and development tumors through oncogenic reprogramming tumor-associated macrophages (TAMs). In this study, we will investigate effect osteosarcoma-derived exosomes on polarization TAMs decipher its underlying mechanism. Osteosarcoma-derived from MG63 cells were isolated characterized by transmission electron microscopy, nano-particle size analysis. Double fluorescence staining was performed to confirm phagocytosis exosomes. Western blot, qRT-PCR, transwell assays conducted assess migration, invasion, macrophage differentiation. The mouse model osteosarcoma established evaluate effects lung metastasis vivo. successfully verified be phagocytized confocal microscopy. results revealed could induce M2 type differentiation largely Tim-3 mediated exosomes, which turn promote epithelial-mesenchymal transition (EMT), secretion cytokines including IL-10, TGF-?, VEGF. Our demonstrated induced promoted invasion Tim-3; besides, study also suggests novel therapeutic target for future studies.