The Irradiated Brain Microenvironment Supports Glioma Stemness and Survival via Astrocyte-Derived Transglutaminase 2.
Animals
Astrocytes
/ enzymology
Brain
/ cytology
Brain Neoplasms
/ pathology
Cell Survival
/ physiology
Enzyme Inhibitors
/ pharmacology
Extracellular Matrix
/ metabolism
Female
GTP-Binding Proteins
/ antagonists & inhibitors
Glioblastoma
/ pathology
Glioma
/ pathology
Humans
Male
Mice
Neoplasm Recurrence, Local
/ enzymology
Neoplastic Stem Cells
/ physiology
Protein Glutamine gamma Glutamyltransferase 2
Radiation Tolerance
Transglutaminases
/ antagonists & inhibitors
Tumor Microenvironment
/ physiology
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
27
05
2020
revised:
02
11
2020
accepted:
19
01
2021
pubmed:
24
1
2021
medline:
14
9
2021
entrez:
23
1
2021
Statut:
ppublish
Résumé
The tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance. Following radiotherapy, recurrent gliomas form in an irradiated microenvironment. Here we report that astrocytes, when pre-irradiated, increase stemness and survival of cocultured glioma cells. Tumor-naïve brains increased reactive astrocytes in response to radiation, and mice subjected to radiation prior to implantation of glioma cells developed more aggressive tumors. Extracellular matrix derived from irradiated astrocytes were found to be a major driver of this phenotype and astrocyte-derived transglutaminase 2 (TGM2) was identified as a promoter of glioma stemness and radioresistance. TGM2 levels increased after radiation
Identifiants
pubmed: 33483373
pii: 0008-5472.CAN-20-1785
doi: 10.1158/0008-5472.CAN-20-1785
doi:
Substances chimiques
Enzyme Inhibitors
0
TGM2 protein, human
0
Protein Glutamine gamma Glutamyltransferase 2
EC 2.3.2.13
Transglutaminases
EC 2.3.2.13
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2101-2115Informations de copyright
©2021 American Association for Cancer Research.
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