Tumor cell network integration in glioma represents a stemness feature

• Verfasst von: Xie, Ruifan [VerfasserIn]
• Verfasst von: Keßler, Tobias [VerfasserIn]
• Verfasst von: Grosch, Julia Katharina [VerfasserIn]
• Verfasst von: Hai, Ling [VerfasserIn]
• Verfasst von: Venkataramani, Varun [VerfasserIn]
• Verfasst von: Huang, Lulu [VerfasserIn]
• Verfasst von: Hoffmann, Dirk C. [VerfasserIn]
• Verfasst von: Solecki, Gergely [VerfasserIn]
• Verfasst von: Ratliff, Miriam [VerfasserIn]
• Verfasst von: Schlesner, Matthias [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Winkler, Frank [VerfasserIn]
• Titel: Tumor cell network integration in glioma represents a stemness feature
• Verf.angabe: 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
• E-Jahr: 2021
• Jahr: May 2021
• Umfang: 13 S.
• Fussnoten: Gesehen am 09.03.2022 ; Published: 15 December 2020
• Titel Quelle: Enthalten in: Neuro-Oncology
• Ort Quelle: Oxford : Oxford Univ. Press, 1999
• Jahr Quelle: 2021
• Band/Heft Quelle: 23(2021), 5, Seite 757-769
• ISSN Quelle: 1523-5866
• DOI: doi:10.1093/neuonc/noaa275
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1795137347

Abstract

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.