Exploring the Role of Osteosarcoma-Derived Extracellular Vesicles in Pre-Metastatic Niche Formation and Metastasis in the 143-B Xenograft Mouse Osteosarcoma Model

摘要

Osteosarcoma is an aggressive bone cancer that frequently metastasizes to the lungs and is the second leading cause of cancer-associated death in children and adolescents. Therefore, deciphering the biological mechanisms that mediate osteosarcoma metastasis is urgently needed in order to develop effective treatment. The aim of our study was to shed light on the primary tumor-induced changes in the lungs prior to osteosarcoma cell arrival using a xenograft osteosarcoma mouse model. Furthermore, we investigated the functional role of osteosarcoma-derived extracellular vesicles in pre-metastatic niche formation and metastasis. We showed that the primary tumor initiates an influx of CD11b+ myeloid cells in the pre-metastatic lungs. Furthermore, we demonstrated that osteosarcoma-derived extracellular vesicles alone can recapitulate myeloid cell infiltration in the lungs of naïve mice, but are insufficient to promote osteosarcoma metastasis. Our findings provide valuable insight into the field of osteosarcoma-derived extracellular vesicles and their role in pre-metastatic niche formation in the 143-B osteosarcoma model.