Håkan Axelson
Research team manager
The Irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived transglutaminase 2
Author
Summary, in English
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 in vivo and in recurrent human glioma, and TGM2 inhibitors abrogated glioma stemness and survival. These data suggest that irradiation of the brain results in the formation of a tumor-supportive microenvironment. Therapeutic targeting of radiation-induced, astrocyte-derived extracellular matrix proteins may enhance the efficacy of standard-of-care radiotherapy by reducing stemness in glioma.
Department/s
- Division of Translational Cancer Research
- LUCC: Lund University Cancer Centre
- Brain Tumor Biology
- Paediatrics (Lund)
- Childhood Cancer Research Unit
- Tumor microenvironment
- Neurosurgery
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
Publishing year
2021-04-01
Language
English
Pages
2101-2115
Publication/Series
Cancer Research
Volume
81
Issue
8
Document type
Journal article
Publisher
American Association for Cancer Research Inc.
Topic
- Cancer and Oncology
Status
Published
Research group
- Brain Tumor Biology
- Childhood Cancer Research Unit
- Tumor microenvironment
ISBN/ISSN/Other
- ISSN: 0008-5472