Journal article
The dystroglycan receptor maintains glioma stem cells in the vascular niche
Acta neuropathologica, Vol.138(6), pp.1033-1052
2019
DOI: 10.1007/s00401-019-02069-x
PMCID: PMC6851226
PMID: 31463571
Abstract
Glioblastomas (GBMs) are malignant central nervous system (CNS) neoplasms with a very poor prognosis. They display cellular hierarchies containing self-renewing tumourigenic glioma stem cells (GSCs) in a complex heterogeneous microenvironment. One proposed GSC niche is the extracellular matrix (ECM)-rich perivascular bed of the tumour. Here, we report that the ECM binding dystroglycan (DG) receptor is expressed and functionally glycosylated on GSCs residing in the perivascular niche. Glycosylated αDG is highly expressed and functional on the most aggressive mesenchymal-like (MES-like) GBM tumour compartment. Furthermore, we found that DG acts to maintain an MES-like state via tight control of MAPK activation. Antibody-based blockade of αDG induces robust ERK-mediated differentiation leading to reduced GSC potential. DG was shown to be required for tumour initiation in MES-like GBM, with constitutive loss significantly delaying or preventing tumourigenic potential in-vivo. These findings reveal a central role of the DG receptor, not only as a structural element, but also as a critical factor promoting MES-like GBM and the maintenance of GSCs residing in the perivascular niche.
Details
- Title: Subtitle
- The dystroglycan receptor maintains glioma stem cells in the vascular niche
- Creators
- Bryan W Day - Brisbane, QLD 4006 AustraliaJustin D Lathia - Cleveland, OH 44195 USAZara C Bruce - Brisbane, QLD 4006 AustraliaRochelle C. J D’Souza - Brisbane, QLD 4006 AustraliaUlrich Baumgartner - Brisbane, QLD 4006 AustraliaKathleen S Ensbey - Brisbane, QLD 4006 AustraliaYi Chieh Lim - Brisbane, QLD 4006 AustraliaBrett W Stringer - Brisbane, QLD 4006 AustraliaSeçkin Akgül - Brisbane, QLD 4006 AustraliaCarolin Offenhäuser - Brisbane, QLD 4006 AustraliaYuchen Li - Brisbane, QLD 4006 AustraliaPaul R Jamieson - Brisbane, QLD 4006 AustraliaFiona M Smith - Brisbane, QLD 4006 AustraliaCourtney L. R Jurd - Brisbane, QLD 4006 AustraliaThomas Robertson - Brisbane, QLD 4006 AustraliaPo-Ling Inglis - Brisbane, QLD 4006 AustraliaZarnie Lwin - Brisbane, QLD 4006 AustraliaRosalind L Jeffree - Brisbane, QLD 4006 AustraliaTerrance G Johns - Perth, WA 6009 AustraliaKrishna P. L Bhat - Houston, TX 77030 USAJeremy N Rich - La Jolla, San Diego, CA 92093-0021 USAKevin P Campbell - Iowa City, IA 52242 USAAndrew W Boyd - Brisbane, QLD 4006 Australia
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica, Vol.138(6), pp.1033-1052
- DOI
- 10.1007/s00401-019-02069-x
- PMID
- 31463571
- PMCID
- PMC6851226
- NLM abbreviation
- Acta Neuropathol
- ISSN
- 0001-6322
- eISSN
- 1432-0533
- Publisher
- Springer Berlin Heidelberg; Berlin/Heidelberg
- Grant note
- ; 1U54NS053672 / ; I.D.1078893 / ;
- Language
- English
- Date published
- 2019
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068377402771
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