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Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma

Tumor-initiating cells contained within the aggressive brain tumor glioma (glioma stem cells, GSCs) promote radioresistance and disease recurrence. However, mechanisms of resistance are not well understood. Herein, we show that the proteome-level regulation occurring upon radiation treatment of seve...

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Autores principales: Panizza, Elena, Regalado, Brandon D, Wang, Fangyu, Nakano, Ichiro, Vacanti, Nathaniel M, Cerione, Richard A, Antonyak, Marc A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10087103/
https://www.ncbi.nlm.nih.gov/pubmed/37037593
http://dx.doi.org/10.26508/lsa.202201680
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author Panizza, Elena
Regalado, Brandon D
Wang, Fangyu
Nakano, Ichiro
Vacanti, Nathaniel M
Cerione, Richard A
Antonyak, Marc A
author_facet Panizza, Elena
Regalado, Brandon D
Wang, Fangyu
Nakano, Ichiro
Vacanti, Nathaniel M
Cerione, Richard A
Antonyak, Marc A
author_sort Panizza, Elena
collection PubMed
description Tumor-initiating cells contained within the aggressive brain tumor glioma (glioma stem cells, GSCs) promote radioresistance and disease recurrence. However, mechanisms of resistance are not well understood. Herein, we show that the proteome-level regulation occurring upon radiation treatment of several patient-derived GSC lines predicts their resistance status, whereas glioma transcriptional subtypes do not. We identify a mechanism of radioresistance mediated by the transfer of the metabolic enzyme NAMPT to radiosensitive cells through microvesicles (NAMPT-high MVs) shed by resistant GSCs. NAMPT-high MVs rescue the proliferation of radiosensitive GSCs and fibroblasts upon irradiation, and upon treatment with a radiomimetic drug or low serum, and increase intracellular NAD(H) levels. Finally, we show that the presence of NAMPT within the MVs and its enzymatic activity in recipient cells are necessary to mediate these effects. Collectively, we demonstrate that the proteome of GSCs provides unique information as it predicts the ability of glioma to resist radiation treatment. Furthermore, we establish NAMPT transfer via MVs as a mechanism for rescuing the proliferation of radiosensitive cells upon irradiation.
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spelling pubmed-100871032023-04-12 Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma Panizza, Elena Regalado, Brandon D Wang, Fangyu Nakano, Ichiro Vacanti, Nathaniel M Cerione, Richard A Antonyak, Marc A Life Sci Alliance Research Articles Tumor-initiating cells contained within the aggressive brain tumor glioma (glioma stem cells, GSCs) promote radioresistance and disease recurrence. However, mechanisms of resistance are not well understood. Herein, we show that the proteome-level regulation occurring upon radiation treatment of several patient-derived GSC lines predicts their resistance status, whereas glioma transcriptional subtypes do not. We identify a mechanism of radioresistance mediated by the transfer of the metabolic enzyme NAMPT to radiosensitive cells through microvesicles (NAMPT-high MVs) shed by resistant GSCs. NAMPT-high MVs rescue the proliferation of radiosensitive GSCs and fibroblasts upon irradiation, and upon treatment with a radiomimetic drug or low serum, and increase intracellular NAD(H) levels. Finally, we show that the presence of NAMPT within the MVs and its enzymatic activity in recipient cells are necessary to mediate these effects. Collectively, we demonstrate that the proteome of GSCs provides unique information as it predicts the ability of glioma to resist radiation treatment. Furthermore, we establish NAMPT transfer via MVs as a mechanism for rescuing the proliferation of radiosensitive cells upon irradiation. Life Science Alliance LLC 2023-04-10 /pmc/articles/PMC10087103/ /pubmed/37037593 http://dx.doi.org/10.26508/lsa.202201680 Text en © 2023 Panizza et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Panizza, Elena
Regalado, Brandon D
Wang, Fangyu
Nakano, Ichiro
Vacanti, Nathaniel M
Cerione, Richard A
Antonyak, Marc A
Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma
title Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma
title_full Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma
title_fullStr Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma
title_full_unstemmed Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma
title_short Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma
title_sort proteomic analysis reveals microvesicles containing nampt as mediators of radioresistance in glioma
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10087103/
https://www.ncbi.nlm.nih.gov/pubmed/37037593
http://dx.doi.org/10.26508/lsa.202201680
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