Extracellular Vesicles Induce Mesenchymal Transition and Therapeutic Resistance in Glioblastomas through NF-κB/STAT3 Signaling

Markus W. Schweiger, Mao Li, Alberta Giovanazzi, Renata L. Fleming, Elie I. Tabet, Ichiro Nakano, Thomas Würdinger, Ennio Antonio Chiocca, Tian Tian, Bakhos A. Tannous*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor and despite optimal treatment, long-term survival remains uncommon. GBM can be roughly divided into three different molecular subtypes, each varying in aggressiveness and treatment resistance. Recent evidence shows plasticity between these subtypes in which the proneural (PN) glioma stem-like cells (GSCs) undergo transition into the more aggressive mesenchymal (MES) subtype, leading to therapeutic resistance. Extracellular vesicles (EVs) are membranous structures secreted by nearly every cell and are shown to play a key role in GBM progression by acting as multifunctional signaling complexes. Here, it is shown that EVs derived from MES cells educate PN cells to increase stemness, invasiveness, cell proliferation, migration potential, aggressiveness, and therapeutic resistance by inducing mesenchymal transition through nuclear factor-κB/signal transducer and activator of transcription 3 signaling. The findings could potentially help explore new treatment strategies for GBM and indicate that EVs may also play a role in mesenchymal transition of different tumor types.

Original languageEnglish
Article number1900312
JournalAdvanced Biosystems
Volume4
Issue number12
DOIs
Publication statusPublished - Dec 2020

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