Interferon-β exposure induces a fragile glioblastoma stem cell phenotype with a transcriptional profile of reduced migratory and MAPK pathway activity.
glioblastoma
interferon
signaling
stemness
transcription
Journal
Neuro-oncology advances
ISSN: 2632-2498
Titre abrégé: Neurooncol Adv
Pays: England
ID NLM: 101755003
Informations de publication
Date de publication:
Historique:
entrez:
10
7
2020
pubmed:
10
7
2020
medline:
10
7
2020
Statut:
epublish
Résumé
Type 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. Repetitive 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. Here 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. Altogether, these data suggest a role for promoting IFN-β signaling in glioblastoma and might provide clues to design future therapeutic approaches.
Sections du résumé
BACKGROUND
BACKGROUND
Type 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.
METHODS
METHODS
Repetitive 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.
RESULTS
RESULTS
Here 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.
CONCLUSIONS
CONCLUSIONS
Altogether, these data suggest a role for promoting IFN-β signaling in glioblastoma and might provide clues to design future therapeutic approaches.
Identifiants
pubmed: 32642697
doi: 10.1093/noajnl/vdaa043
pii: vdaa043
pmc: PMC7212887
doi:
Types de publication
Journal Article
Langues
eng
Pagination
vdaa043Informations de copyright
© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
Références
Blood Cancer J. 2014 Feb 14;4:e184
pubmed: 24531447
Trends Cell Biol. 2018 Jun;28(6):436-453
pubmed: 29477613
N Engl J Med. 2005 Mar 10;352(10):997-1003
pubmed: 15758010
Cancer. 2011 Apr 15;117(8):1721-30
pubmed: 21472719
Cell Death Dis. 2014 Nov 20;5:e1528
pubmed: 25412306
Mol Cancer Ther. 2014 Apr;13(4):948-61
pubmed: 24526161
N Engl J Med. 2014 Feb 20;370(8):699-708
pubmed: 24552317
Oncotarget. 2017 Aug 3;8(50):87124-87135
pubmed: 29152068
Cell. 2013 Apr 11;153(2):471-9
pubmed: 23582332
N Engl J Med. 2001 Dec 6;345(23):1655-9
pubmed: 11759643
N Engl J Med. 1984 Jan 5;310(1):15-8
pubmed: 6689734
J Biol Chem. 1986 Jan 5;261(1):453-9
pubmed: 2934388
Mol Cell Biol. 2009 Sep;29(17):4841-51
pubmed: 19564419
Science. 2011 Mar 25;331(6024):1565-70
pubmed: 21436444
Nature. 2007 Dec 6;450(7171):903-7
pubmed: 18026089
Lancet. 1979 Sep 29;2(8144):697
pubmed: 90788
Cell. 1997 Mar 7;88(5):593-602
pubmed: 9054499
N Engl J Med. 1986 Apr 24;314(17):1065-9
pubmed: 3457264
Nat Immunol. 2005 Jul;6(7):722-9
pubmed: 15951814
Cancer Immunol Immunother. 1997 Mar;44(1):55-63
pubmed: 9111585
J Neurooncol. 2018 Jul;138(3):627-636
pubmed: 29557060
Immunol Rev. 2004 Dec;202:8-32
pubmed: 15546383
Development. 2018 Feb 26;145(4):
pubmed: 29483129
Neuro Oncol. 2017 Nov 6;19(suppl_5):v1-v88
pubmed: 29117289
Am J Physiol Heart Circ Physiol. 2008 Mar;294(3):H1119-29
pubmed: 18203850
N Engl J Med. 1990 May 17;322(20):1430-4
pubmed: 2184356
Exp Gerontol. 2003 Aug;38(8):887-95
pubmed: 12915210
Nat Rev Immunol. 2015 Jul;15(7):405-14
pubmed: 26027717
J Am Acad Dermatol. 2013 Feb;68(2):313-31
pubmed: 22695100
Aging Cell. 2006 Apr;5(2):187-95
pubmed: 16626397
PLoS One. 2014 Oct 23;9(10):e110969
pubmed: 25340529
Genes Dev. 2009 Apr 1;23(7):798-803
pubmed: 19279323
Cancer Res. 2008 Jul 15;68(14):5658-68
pubmed: 18632618
Curr Opin Cell Biol. 2010 Apr;22(2):234-40
pubmed: 20045302
J Neurooncol. 2011 Sep;104(2):573-7
pubmed: 21327711
Lancet Oncol. 2017 Jun;18(6):e315-e329
pubmed: 28483413
Biochem Biophys Res Commun. 2007 Dec 28;364(4):808-14
pubmed: 17977513
Br J Cancer. 2009 Aug 18;101(4):615-20
pubmed: 19672263
J Neurochem. 2012 Jul;122(2):444-55
pubmed: 22564186
Clin Cancer Res. 2019 Mar 15;25(6):1809-1816
pubmed: 30514777
Nat Rev Immunol. 2005 May;5(5):375-86
pubmed: 15864272
Int J Cancer. 2019 Jul 1;145(1):242-253
pubmed: 30549269
Cancer. 2016 Jul 15;122(14):2206-15
pubmed: 27088883
Biochem J. 2006 Jul 1;397(1):31-8
pubmed: 16551269
Lancet Oncol. 2017 Oct;18(10):1373-1385
pubmed: 28844499
J Exp Med. 2010 Sep 27;207(10):2053-63
pubmed: 20837696
Cancer Res. 2005 Sep 1;65(17):7573-9
pubmed: 16140920
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
N Engl J Med. 2014 Feb 20;370(8):709-22
pubmed: 24552318