| Literature DB >> 33579922 |
Erik Jung1,2, Matthias Osswald1,2, Miriam Ratliff2,3, Helin Dogan4,5, Ruifan Xie1,2, Sophie Weil1,2, Dirk C Hoffmann1,2, Felix T Kurz6, Tobias Kessler1,2, Sabine Heiland6, Andreas von Deimling4,5, Felix Sahm4,5, Wolfgang Wick1,2, Frank Winkler7,8.
Abstract
Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy-independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted.Entities:
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Year: 2021 PMID： 33579922 PMCID： PMC7881116 DOI： 10.1038/s41467-021-21117-3
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919