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Tumor cell network integration in glioma represents a stemness feature
- Source :
- Neuro Oncol
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- 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.
- Subjects :
- Cancer Research
Brain tumor
Biology
Nestin
In vivo
Cancer stem cell
Cell Line, Tumor
Glioma
Radioresistance
Gene expression
medicine
Humans
ddc:610
neoplasms
Brain Neoplasms
Brain
Cell sorting
medicine.disease
Oncology
Basic and Translational Investigations
Neoplastic Stem Cells
Cancer research
Neurology (clinical)
Glioblastoma
Subjects
Details
- ISSN :
- 15235866 and 15228517
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....5920e2509adf55d8370d80314ffbd26e