The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma.
Animals
Astrocytoma
/ mortality
Brain Neoplasms
/ mortality
Cell Proliferation
Cellular Senescence
Child
Culture Media, Conditioned
/ metabolism
Datasets as Topic
Disease Models, Animal
Female
Gene Expression Profiling
Humans
Interleukin-1beta
/ metabolism
Male
Mice
Primary Cell Culture
Prognosis
Progression-Free Survival
Tumor Cells, Cultured
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
20
06
2018
revised:
02
11
2018
accepted:
04
12
2018
pubmed:
12
12
2018
medline:
28
5
2020
entrez:
12
12
2018
Statut:
ppublish
Résumé
Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown. SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted.
Identifiants
pubmed: 30530705
pii: 1078-0432.CCR-18-1965
doi: 10.1158/1078-0432.CCR-18-1965
doi:
Substances chimiques
Culture Media, Conditioned
0
IL1B protein, human
0
Interleukin-1beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1851-1866Subventions
Organisme : Medical Research Council
ID : MR/M000125/1
Pays : United Kingdom
Informations de copyright
©2018 American Association for Cancer Research.