Interferon-β exposure induces a fragile glioblastoma stem cell phenotype with a transcriptional profile of reduced migratory and MAPK pathway activity
| Autor: | Birthe Lohmann, Guido Reifenberger, Daniel Picard, Michael Weller, Hannah Schneider, Manuela Silginer, Patrick Roth, Marc Remke |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway 610 Medicine & health stemness 03 medical and health sciences 0302 clinical medicine Interferon medicine STAT1 biology glioblastoma Cell migration interferon 10040 Clinic for Neurology Cell biology 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Basic and Translational Investigations biology.protein Stem cell Signal transduction signaling transcription Interferon type I medicine.drug |
| Zdroj: | Neuro-oncology Advances |
| ISSN: | 2632-2498 |
| Popis: | BackgroundType I interferons (IFN-α/β) are cytokines that are typically expressed in response to double-stranded RNA associated with viral infections. Glioblastomas are the most common malignant primary brain tumors, characterized by an infiltrative growth pattern and prominent angiogenic activity, and thought to be maintained by a subpopulation of glioma-initiating (stem-like) cells (GICs). The growth of human GIC lines is highly sensitive to IFN-β.MethodsRepetitive pulse stimulation with IFN-β1a (IS) was used to generate IS sublines that had acquired resistance to IFN-β-induced suppression of sphere formation. These cell lines were characterized by analyses of type 1 IFN signaling, growth patterns, and transcriptomic profiles.ResultsHere we report that repetitive IFN-β1a stimulation (IS) induces a stable phenotype (referred to as IS) at the level of maintaining sphere formation, although classical IFN signaling defined by the expression of both IFN receptors, myxovirus resistance protein A (MxA) accumulation, and STAT1 induction is unaffected. Furthermore, this stably altered IS phenotype is characterized by constitutively decreased sphere formation capacity and morphological features of senescence and autophagy. Transcriptional profiling reveals increased type I IFN signaling in these IS cells, but decreased expression of genes involved in receptor signaling and cell migration.ConclusionsAltogether, these data suggest a role for promoting IFN-β signaling in glioblastoma and might provide clues to design future therapeutic approaches. |
| Databáze: | OpenAIRE |
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