Exosomes as Novel Diagnostic Biomarkers and Therapeutic Tools in Gliomas

Abstract

Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of transmitting signals between cells and coordinating cellular communication. By this means, they are ultimately involved in physiology and disease, including development, homeostasis, and immune system regulation, as well as contributing to tumor progression and neurodegenerative diseases pathology. Recent studies have shown that gliomas secrete a panel of exosomes which have been associated with cell invasion and migration, tumor immune tolerance, potential for malignant transformation, neovascularization, and resistance to treatment. Exosomes have therefore emerged as intercellular communicators, which mediate the tumor-microenvironment interactions and exosome-regulated glioma cell stemness and angiogenesis. They may induce tumor proliferation and malignancy in normal cells by carrying pro-migratory modulators from cancer cells as well as many different molecular cancer modifiers, such as oncogenic transcripts, miRNAs, mutant oncoproteins, etc., which promote the communication of cancer cells with the surrounding stromal cells and provide valuable information on the molecular profile of the existing tumor. Moreover, engineered exosomes can provide an alternative system for drug delivery and enable efficient treatment. In the present review, we discuss the latest findings regarding the role of exosomes in glioma pathogenesis, their utility in non-invasive diagnosis, and potential applications to treatment.

Keywords: brain tumors; drug delivery; exosome; extracellular vesicles; glioblastoma; glioma.

Figure 1

The role of exosomes in glioma pathogenesis and treatment. Exosomes derived from glioma cells mediate the interactions of cancer cells with the tumor microenvironment and facilitate certain malignant properties. Exosomes can be used as diagnostic and therapeutic tools since they can be non-invasively detected in blood samples and cerebrospinal fluid. They have been also suggested as potential drug delivery systems (figure created using BioRender.com, accessed on 16 May 2023).

Figure 2

The exosome biogenesis pathway. Early endosomes could follow the ESCRT-dependent exosome pathway to form MVBs. MVBs can either follow the lysosomal pathway or form and secrete exosomes. There are also alternative ESCRT-independent ways of exosome biogenesis though ceramide, tetraspanins, and SNARE proteins. ESCRT, endosomal sorting complex required for transport; MVB, multivesicular bodies; SNARE, SNAP receptor (figure created using BioRender.com, accessed on 7 June 2023).