Tumor cell network integration in glioma represents a stemness feature.
cancer stem cells
glioblastoma
glioma
networks
tumor microtubes
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
pubmed:
16
12
2020
medline:
21
5
2021
entrez:
15
12
2020
Statut:
ppublish
Résumé
Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes a subpopulation of glioma cells that becomes highly resistant by integration into tumor microtube (TM)-connected multicellular networks. A novel functional approach to detect, isolate, and characterize glioma cell subpopulations with respect to in vivo network integration is established, combining a dye staining method with intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular profiling, and gene reporter studies. Glioblastoma cells that are part of the TM-connected tumor network show activated neurodevelopmental and glioma progression gene expression pathways. Importantly, many of them revealed profiles indicative of increased cellular stemness, including high expression of nestin. TM-connected glioblastoma cells also had a higher potential for reinitiation of brain tumor growth. Long-term tracking of tumor cell nestin expression in vivo revealed a stronger TM network integration and higher radioresistance of the nestin-high subpopulation. Glioblastoma cells that were both nestin-high and network-integrated were particularly able to adapt to radiotherapy with increased TM formation. Multiple stem-like features are strongly enriched in a fraction of network-integrated glioma cells, explaining their particular resilience.
Sections du résumé
BACKGROUND
Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes a subpopulation of glioma cells that becomes highly resistant by integration into tumor microtube (TM)-connected multicellular networks.
METHODS
A novel functional approach to detect, isolate, and characterize glioma cell subpopulations with respect to in vivo network integration is established, combining a dye staining method with intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular profiling, and gene reporter studies.
RESULTS
Glioblastoma cells that are part of the TM-connected tumor network show activated neurodevelopmental and glioma progression gene expression pathways. Importantly, many of them revealed profiles indicative of increased cellular stemness, including high expression of nestin. TM-connected glioblastoma cells also had a higher potential for reinitiation of brain tumor growth. Long-term tracking of tumor cell nestin expression in vivo revealed a stronger TM network integration and higher radioresistance of the nestin-high subpopulation. Glioblastoma cells that were both nestin-high and network-integrated were particularly able to adapt to radiotherapy with increased TM formation.
CONCLUSION
Multiple stem-like features are strongly enriched in a fraction of network-integrated glioma cells, explaining their particular resilience.
Identifiants
pubmed: 33320195
pii: 6035154
doi: 10.1093/neuonc/noaa275
pmc: PMC8099480
doi:
Substances chimiques
Nestin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
757-769Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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