Exosomes in osteosarcoma research and preclinical practice

Abstract

Osteosarcoma (OS) is a rare soft-tissue malignant tumor with high lung metastasis and mortality rates. Preoperative chemotherapy, surgical resection of the lesion and postoperative chemotherapy are still the main treatments for osteosarcoma. The prognosis, however, is poor for patients with nonresectable, primary metastatic or relapsed disease. Recent studies have shown that targeted therapy for OS based on the characteristics of exosomes is very attractive. Exosomes are nanosized extracellular vesicles (EVs) that participate in cell-to-cell communication by transporting biologically active cargo molecules, causing changes in OS cell function and playing important roles in OS disease progression. With the characteristics of secretory cells, exosomes transport cargo (e.g., microRNAs) that can be used to detect the progress of a disease and can serve as markers and/or therapeutic targets for clinical diagnosis of OS. In this review, the roles of exosomes in OS pathogenesis, invasion, metastasis, drug resistance, diagnosis and treatment are summarized. In addition, this article elaborates a series of challenges to overcome before exosomes are applied in clinical practice and provides suggestions based on current evidence for the direction of future research.

Keywords: Osteosarcoma (OS); challenges; exosomes; microRNA (miRNA).

Figure 1

Exosome biogenesis begins with invagination of the endosomal membrane to form intracellular vesicles. In late endosomes, inward protrusion of the endosomal membrane leads to accumulation of small vesicles, thereby transforming the endosome into multiple multivesicular bodies (MVBs). MVBs can enter the degradation pathway upon maturation into lysosomes or can be released as exosomes into the extracellular system upon fusion with the plasma membrane.

Figure 2

Exosomes interact with receptor cells through three mechanisms: 1) release of their cargo after entry into the cell via endocytosis; 2) direct fusion with the plasma membrane to nonselectively release the protein and small RNA molecules contained within; and 3) interaction with exosome ligands and receptor proteins on the cell membrane surface.

Figure 3

Exosomes carrying genetic materials participate in the development of osteosarcoma by promoting angiogenesis, invasion and metastasis, immune escape and drug resistance.