Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

Abstract

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

Keywords: extracellular vesicles; osteosarcoma; therapy.

Figure 1

Extracellular vesicles (EVs). EVs represent a heterogeneous population of vesicles, including microvesicles and exosomes, differing in size, content and biogenesis. Microvesicles (up to 1 µm) are produced by direct outward budding of the cell membrane; exosomes are small vesicles (30–150 nm) and are released by fusion of multivesicular bodies (MVBs) with the plasma membrane into the extracellular space. Figure created using Servier Medical Art (https://smart.servier.com; accessed on 1 October 2021).

Figure 2

Extracellular vesicles as a vehicle for delivering chemotherapeutic drugs. Figure created using Servier Medical Art (https://smart.servier.com; accessed on 1 October 2021).