Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma

Erik Jung, Matthias Osswald, Miriam Ratliff, Helin Dogan, Ruifan Xie, Sophie Weil, Dirk C. Hoffmann, Felix T. Kurz, Tobias Kessler, Sabine Heiland, Andreas Deimling, Felix Sahm, Wolfgang Wick and Frank Winkler ()
Additional contact information
Erik Jung: University Hospital Heidelberg
Matthias Osswald: University Hospital Heidelberg
Miriam Ratliff: German Cancer Research Center (DKFZ)
Helin Dogan: Ruprecht-Karls University Heidelberg
Ruifan Xie: University Hospital Heidelberg
Sophie Weil: University Hospital Heidelberg
Dirk C. Hoffmann: University Hospital Heidelberg
Felix T. Kurz: University Hospital Heidelberg
Tobias Kessler: University Hospital Heidelberg
Sabine Heiland: University Hospital Heidelberg
Andreas Deimling: Ruprecht-Karls University Heidelberg
Felix Sahm: Ruprecht-Karls University Heidelberg
Wolfgang Wick: University Hospital Heidelberg
Frank Winkler: University Hospital Heidelberg

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21117-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21117-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21117-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().