Extracellular Vesicles Induce Mesenchymal Transition and Therapeutic Resistance in Glioblastomas through NF‐κB/STAT3 Signaling
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- Markus W. Schweiger
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
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- Mao Li
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
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- Alberta Giovanazzi
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
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- Renata L. Fleming
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
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- Elie I. Tabet
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
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- Ichiro Nakano
- Department of Neurosurgery and Comprehensive Cancer Center University of Alabama at Birmingham Birmingham AL 35233 USA
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- Thomas Würdinger
- Department of Neurosurgery Cancer Center Amsterdam Brain Tumor Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam 1081 HV The Netherlands
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- Ennio Antonio Chiocca
- Department of Neurosurgery Brigham and Women's Hospital Boston MA 02115 USA
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- Tian Tian
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
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- Bakhos A. Tannous
- Experimental Therapeutics and Molecular Imaging Laboratory Department of Neurology Neuro‐Oncology Division, Massachusetts General Hospital Boston MA 02129 USA
説明
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
収録刊行物
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- Advanced Biosystems
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Advanced Biosystems 4 (12), e1900312-, 2020-06-09
Wiley