The Dystroglycan Receptor Maintains Glioma Stem Cells in the Vascular Niche

Overview

Journal Acta Neuropathol

Specialty Neurology

Date 2019 Aug 30

PMID 31463571

Citations 17

Authors

Bryan W Day

Justin D Lathia

Zara C Bruce

Rochelle C J DSouza

Ulrich Baumgartner

Kathleen S Ensbey

Yi Chieh Lim

Brett W Stringer

Seckin Akgul

Carolin Offenhauser

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

Affiliations

Soon will be listed here.

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.

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