Breaking through the glioblastoma micro-environment via extracellular vesicles

Georgios Giamas,Thomas Simon,Ellen Jackson

doi:10.1038/s41388-020-1308-2

Abstract

Glioblastoma (GBM) is the most common and most aggressive brain tumour. Prognosis remains poor, despite the combined treatment of radio- and chemotherapy following surgical removal. GBM cells coexist with normal non-neoplastic cells, including endothelial cells, astrocytes and immune cells, constituting a complex and dynamic tumour micro-environment (TME). Extracellular vesicles (EVs) provide a critical means of bidirectional inter-cellular communication in the TME. Through delivery of a diverse range of genomic, lipidomic and proteomic cargo to neighbouring and distant cells, EVs can alter the phenotype and function of the recipient cell. As such, EVs have demonstrated their role in promoting angiogenesis, immune suppression, invasion, migration, drug resistance and GBM recurrence. Moreover, EVs can reflect the phenotype of the cells within the TME. Thus, in conjunction with their accessibility in biofluids, they can potentially serve as a biomarker reservoir for patient prognosis, diagnosis and predictive therapeutic response as well as treatment follow-up. Furthermore, together with the ability of EVs to cross the blood–brain barrier undeterred and through the exploitation of their cargo, EVs may provide an effective mean of drug delivery to the target site. Unveiling the mechanisms by which EVs within the GBM TME are secreted and target recipient cells may offer an indispensable understanding of GBM that holds the potential to provide a better prognosis and overall quality of life for GBM patients.

Highlights

Glioblastoma (GBM) is the most common, aggressive primary adult brain tumour, leaving patients with a median survival rate of 15 months after treatment, while displaying a high recurrence rate and resistance to therapeutics [1]
The current treatment for GBM patients includes maximal surgical resection followed by radiotherapy with temozolomide (TMZ), an oral alkylating chemotherapy drug [2]
Extracellular vesicles (EVs) containing miR-1 transferred between GBM cells and the tumour micro-environment (TME) have been shown to have tumour suppressive effects, decreasing angiogenesis, tumourigenicity and invasion in vitro and in vivo [16]

Summary

Introduction

Glioblastoma (GBM) is the most common, aggressive primary adult brain tumour, leaving patients with a median survival rate of 15 months after treatment, while displaying a high recurrence rate and resistance to therapeutics [1]. EVs containing miR-1 transferred between GBM cells and the TME have been shown to have tumour suppressive effects, decreasing angiogenesis, tumourigenicity and invasion in vitro and in vivo [16].

Results

Conclusion