Extracellular Vesicles Involvement in the Modulation of the Glioblastoma Environment

Abstract

Glioblastoma (GBM) is the most deadly primary brain tumour and is a paradigmatic example of heterogeneous cancer. Although expanding data propose the phenotypic plasticity exhibited by glioblastoma cells, as a critical feature involved in the tumour development and posttherapy recurrence, the central machinery responsible for their aggressiveness remains elusive. Despite decades of research, the complex biology of the glioblastoma is still unknown. Progress in genetic and epigenetic discoveries has improved diagnostic classification, prognostic information, and therapeutic planning. In the complex model of intercellular signalling, several studies have shown that extracellular vesicles have a key role in the intercellular communication among GBM cells and the tumour microenvironment modulation. The purpose of this review is to summarize the role of the EV-mediated intercellular crosstalk in the glioblastoma physiopathology.

Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma

“…Although multiple drug delivery vehicles (liposome, polymeric nanoparticle, solid lipid, and polymeric micelle) have been developed in cancer therapy, it is very challengeable to use these synthesized nanoparticles in GBM treatment due to the issues of stability and/or the BBB [ 29 ]. As a natural vesicle, EV has multiple advantages over the synthesized particles, including low immune toxicity, high stability, and efficient penetration of the BBB [ 36 , 37 ]. This study used our established biomanufacturing platform [ 28 , 38 ] to generate EV from human cell line, surface-tagged mAb, and the packed drug Ver-A, which demonstrated the capabilities of high GBM targeting and effective drug delivery.…”

“…These delivery vehicles have been limited in clinic application due to the poor stability, limited loading capacity, toxicity or reduced efficacy because of BBB. Recent studies showed that extracellular vesicle (EV), a natural endogenous nanoparticle, has great potential for targeted delivery of highly potent drugs with the advantages of immune tolerance, circulation stability, capability to cross BBB, and tumor targeting via surface-tagged GBM-targeted reagents [ 36 , 37 ]. Our previous studies have established the platform of EV biomanufacturing and surface tagging [ 38 ] and demonstrated its capability of targeted delivery of combined therapies [ 28 ].…”

A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas

“…This suggested that macrophages could change the tumor microenvironment to promote cell invasion and mediate the paraptosis by oxidative stress in glioma cells. Extracellular vesicles have multiple functions in the central nervous system and are closely related to the communication between cell types within glioblastoma and their microenvironment [ 29 ]. Glioblastoma-induced exosomes can increase the oxidative stress of cerebellar neurons by reducing cellular antioxidant defense and increasing oxidative damage [ 30 ].…”

Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes

“…Several studies have shown that EVs, signaling vehicles with multifaceted functions in neuronal and glial crosstalk, have a crucial role in the communication among cell types within glioblastoma and its microenvironment [34,35]. EVs are membrane-enclosed nanospheres that contain proteins, lipids, and nucleic acids, such as DNA, mRNA, and noncoding RNAs, and are released by most cells [36,37].…”