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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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Main Authors: Xie, Ruifan (Author) , Keßler, Tobias (Author) , Grosch, Julia Katharina (Author) , Hai, Ling (Author) , Venkataramani, Varun (Author) , Huang, Lulu (Author) , Hoffmann, Dirk C. (Author) , Solecki, Gergely (Author) , Ratliff, Miriam (Author) , Schlesner, Matthias (Author) , Wick, Wolfgang (Author) , Winkler, Frank (Author)
Format: Article (Journal)
Language:English
Published: May 2021
In: Neuro-Oncology
Year: 2021, Volume: 23, Issue: 5, Pages: 757-769
ISSN:1523-5866
DOI:10.1093/neuonc/noaa275
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noaa275
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 09.03.2022
Published: 15 December 2020
Physical Description:Online Resource
ISSN:1523-5866
DOI:10.1093/neuonc/noaa275

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