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Interferon-? exposure induces a fragile glioblastoma stem cell phenotype with a transcriptional profile of reduced migratory and MAPK pathway activity.

ABSTRACT: AbstractBackgroundType I interferons (IFN-?/?) 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-?.MethodsRepetitive pulse stimulation with IFN-?1a (IS) was used to generate IS sublines that had acquired resistance to IFN-?-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-?1a 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-? signaling in glioblastoma and might provide clues to design future therapeutic approaches.

SUBMITTER: Lohmann B

PROVIDER: S-EPMC7212887 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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