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: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 2021
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| 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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| 245 | 1 | 0 | |a Tumor cell network integration in glioma represents a stemness feature |c 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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| 520 | |a 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. | ||
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