The role of extracellular vesicles in glioblastoma: insights into tumor microenvironment dynamics

Glioblastoma (GBM), the deadliest primary brain tumor in adults, poses a formidable challenge due to its aggressive growth and resistance to therapy. Current treatments, including surgery, radiation, and chemotherapy, often fall short in combating this relentless disease. A recent study sheds light on a key player in GBM progression: extracellular vesicles (EVs), tiny packages secreted by tumor cells that orchestrate communication within the tumor microenvironment.

Researchers at Istituto Superiore di Sanità isolated EVs from two key players in GBM progression: GBM stem-like cells (GSCs) and human microvascular endothelial cells (HMVECs), both before and after exposure to ionizing radiation. Through advanced RNA sequencing techniques, they uncovered a treasure trove of genetic information carried within these EVs.

Two standout transcripts, Periostin (POSTN) and Filamin-B (FLNB), emerged as potential mediators of EV-induced effects on GBM and endothelial cell behavior. POSTN, enriched in EVs from irradiated HMVECs, demonstrated the ability to promote tumor cell migration and clonogenicity. On the other hand, FLNB, found in EVs from irradiated GSCs, played a role in endothelial cell senescence and migration.

Schematic drawing of EV mediated GSC-endothelial cell communication

Fig. 7

Radiation increased EV release and modified EV content in both GSCs and endothelial cells. Filamin-B mediates the effects of GSC-derived EVs on senescence-induced radiation and endothelial cell migration. Periostin mediates the effects of endothelial cell-derived EVs on GSC tumorigenic properties.

These findings underscore the pivotal role of EVs in shaping the tumor microenvironment and driving GBM progression. By shuttling bioactive molecules between cells, EVs act as messengers, fueling the growth and spread of tumors. Understanding the mechanisms behind EV-mediated communication opens new avenues for targeted therapies aimed at disrupting these harmful interactions.

Castellani G, Buccarelli M, D’Alessandris QG, Ilari R, Cappannini A, Pedini F, Boe A, Lulli V, Parolini I, Giannetti S, Biffoni M, Zappavigna V, Marziali G, Pallini R, Ricci-Vitiani L. (2024) Extracellular vesicles produced by irradiated endothelial or Glioblastoma stem cells promote tumor growth and vascularization modulating tumor microenvironment. Cancer Cell Int 24(1):72. [article]

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