Extracellular vesicles: A new diagnostic biomarker and targeted drug in osteosarcoma

Abstract

Osteosarcoma (OS) is a primary bone cancer that is highly prevalent among adolescents and adults below the age of 20 years. The prognostic outcome of metastatic OS or relapse is extremely poor; thus, developing new diagnostic and therapeutic strategies for treating OS is necessary. Extracellular vesicles (EVs) ranging from 30-150 nm in diameter are commonly produced in different cells and are found in various types of body fluids. EVs are rich in biologically active components like proteins, lipids, and nucleic acids. They also strongly affect pathophysiological processes by modulating the intercellular signaling pathways and the exchange of biomolecules. Many studies have found that EVs influence the occurrence, development, and metastasis of osteosarcoma. The regulation of inflammatory communication pathways by EVs affects OS and other bone-related pathological conditions, such as osteoarthritis and rheumatoid arthritis. In this study, we reviewed the latest findings related to diagnosis, prognosis prediction, and the development of treatment strategies for OS from the perspective of EVs.

Keywords: EVs; biomarkers; diagnosis; osteosarcoma; treatment.

Figure 1

Major exosome release process in OS. EVs are comprised of various proteins and nucleic acids. These evolutionarily conserved proteins that can be used as biomarkers, like HSP70, CD9, CD63, and CD81. Additionally, exosomal cargos are also involved in transport of multiple biomolecules such as DNA or RNA. EVs that carry genetic materials are utilized in development of treatment for OS through enhancing drug resistance, immune evasion, migration, invasion, and angiogenesis. Source cell-derived exosomal cargos are also carried into recipient cells via blood circulation. Highly invasive OS cells enhance cell migration and invasion through production of exosomes.

Figure 2

EVs have potential applications in treatment of OS. EVs are multifunctional nanostructured carriers which can be used as drug delivery systems with low immunogenicity as well as high biocompatibility and efficacy. OS-derived EVs contain immunomodulation properties that significantly reduces T cell proliferation rates and promote T regulatory phenotypes, thereby promoting OS progression. OS cases showing low chemosensitivity in patients showing favorable chemosensitivity. miR-9, miR-27a, miR-135b and miR-148a show marked up-regulation within serum EVs of OS patients. OS cells could promote osteosarcoma lung metastasis by releasing EVs that contained PD-L1 and N-calcineurin. EVs from cisplatin-resistant (CDDP)-resistant OS cells decreased P-glycoprotein and MDR-associated protein 1 levels in MG63 and U2OS cells, increases cellular sensitivity to CDDP and inhibits apoptosis through exosomal-hsa_circ_103801.