Year: 2019
Type: article
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.
Source: Acta Neuropathologica
Authors: Bryan W. Day, Justin D. Lathia, Zara C. Bruce, Rochelle C. J. D’Souza, Ulrich Baumgartner, Kathleen S. Ensbey, Yi Chieh Lim, Brett W. Stringer, Seçkin Akgül, Carolin Offenhäuser, Yuchen Li, Paul R. Jamieson, Fiona M. Smith, Courtney L. R. Jurd, Thomas Robertson, Po-Ling Inglis, Zarnie Lwin, Rosalind L. Jeffree, Terrance G. Johns, Krishna P. L. Bhat, Jeremy N. Rich, Kevin P. Campbell, Andrew W. Boyd
Institutions: Queensland University of Technology, The University of Queensland, QIMR Berghofer Medical Research Institute, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Royal Brisbane and Women's Hospital, The Kids Research Institute Australia, The University of Texas MD Anderson Cancer Center, University of California San Diego, University of Iowa, Howard Hughes Medical Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
OpenAlex ID: W2970735504