Dynamic Intercell Communication between Glioblastoma and Microenvironment through Extracellular Vesicles

Abstract

Glioblastoma is simultaneously the most common and most aggressive primary brain tumor in the central nervous system, with poor patient survival and scarce treatment options. Most primary glioblastomas reoccur and evolve radio- and chemoresistant properties which make them resistant to further treatments. Based on gene mutations and expression profiles, glioblastoma is relatively well classified; however, research shows that there is more to glioblastoma biology than that defined solely by its genetic component. Specifically, the overall malignancy of the tumor is also influenced by the dynamic communication to its immediate and distant environment, as important messengers to neighboring cells in the tumor microenvironment extracellular vesicles (EVs) have been identified. EVs and their cargo can modulate the immune microenvironment and other physiological processes, and can interact with the host immune system. They are involved in tumor cell survival and metabolism, tumor initiation, progression, and therapy resistance. However, on the other hand EVs are thought to become an effective treatment alternative, since they can cross the blood–brain barrier, are able of specific cell-targeting and can be loaded with various therapeutic molecules.

Extracellular vesicles, the emerging mirrors of brain physiopathology

“…A growing body of evidence suggests that gliomas can influence cells both nearby and beyond the BBB through the regulated excretion of EVs 178 . In GBMs, the EV content reflects the tumor's unique signature of EGFRvIII mutation, EGFR amplification, TGF-β, IDH1 mutation R132H and podoplanin status 7 .…”

Advancements and Technical Considerations for Extracellular Vesicle Isolation and Biomarker Identification in Glioblastoma

“…20,21 Initially believed to contribute primarily to the disposal of cellular waste, EVs are now recognized as crucial components of intercellular communication and signaling, particularly in the tumor microenvironment. 19,22,23 Microvesicles, apoptotic bodies, and oncosomes bud directly from the plasma membrane. Whereas, exosomes are derived from intraluminal vesicles within multivesicular endosomes, with communication to and from the Golgi body/ endoplasmic reticulum.…”