Buchumschlag

Tumor cell network integration in glioma represents a stemness feature

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...

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Hauptverfasser: Xie, Ruifan (VerfasserIn) , Keßler, Tobias (VerfasserIn) , Grosch, Julia Katharina (VerfasserIn) , Hai, Ling (VerfasserIn) , Venkataramani, Varun (VerfasserIn) , Huang, Lulu (VerfasserIn) , Hoffmann, Dirk C. (VerfasserIn) , Solecki, Gergely (VerfasserIn) , Ratliff, Miriam (VerfasserIn) , Schlesner, Matthias (VerfasserIn) , Wick, Wolfgang (VerfasserIn) , Winkler, Frank (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: May 2021
In: Neuro-Oncology
Year: 2021, Jahrgang: 23, Heft: 5, Pages: 757-769
ISSN:1523-5866
DOI:10.1093/neuonc/noaa275
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noaa275
Volltext
Verfasserangaben:Ruifan Xie, Tobias Kessler, Julia Grosch, Ling Hai, Varun Venkataramani, Lulu Huang, Dirk C Hoffmann, Gergely Solecki, Miriam Ratliff, Matthias Schlesner, Wolfgang Wick, Frank Winkler
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 09.03.2022
Published: 15 December 2020
Beschreibung:Online Resource
ISSN:1523-5866
DOI:10.1093/neuonc/noaa275

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