The Irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived transglutaminase 2

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Bibtex

@article{3f4b54b79e9d44cb873383f629c28320,
title = "The Irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived transglutaminase 2",
abstract = "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-na{\"i}ve 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. ",
author = "Berg, {Tracy J.} and Carolina Marques and Vasiliki Pantazopoulou and Elinn Johansson and {Von Stedingk}, Kristoffer and David Lindgren and Pauline Jeannot and Pietras, {Elin J.} and Tobias Bergstr{\"o}m and Swartling, {Fredrik J.} and Valeria Governa and Johan Bengzon and Mattias Belting and H{\aa}kan Axelson and Massimo Squatrito and Alexander Pietras",
year = "2021",
month = apr,
day = "1",
doi = "10.1158/0008-5472.CAN-20-1785",
language = "English",
volume = "81",
pages = "2101--2115",
journal = "Cancer Research",
issn = "1538-7445",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}