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Cancer Investigation Volume 37, 2019 - Issue 3
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Original Articles

Targeting Glioma Stem Cells by Functional Inhibition of Dynamin 2: A Novel Treatment Strategy for Glioblastoma

Rodney LuworDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; View further author information
,
Andrew P. MorokoffDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; ;Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Australia; View further author information
,
Stephanie AmiridisDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; ;Department of Medicine, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; View further author information
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Giovanna D’AbacoMelbourne School of Engineering, School of Chemical and Biomedical Engineering, The University of Melbourne, Parkville, Australia; View further author information
,
Lucia ParadisoDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; View further author information
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Stanley S. StylliDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; ;Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Australia; View further author information
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Hong P. T. NguyenDepartment of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; View further author information
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Mark TarletonDepartment of Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia; View further author information
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Kelly A. YoungDepartment of Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia; View further author information
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Terence J. O’BrienDepartment of Medicine, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; ;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; ;Department of Neurology, The Alfred Hospital, Melbourne, Australia; View further author information
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Phillip J. RobinsonDepartment of Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia; ;Children’s Medical Research Institute, The University of Sydney, Westmead, AustraliaORCID Iconhttp://orcid.org/0000-0002-7878-0313View further author information
ORCID Icon,
Megan ChircopDepartment of Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia; ;Children’s Medical Research Institute, The University of Sydney, Westmead, AustraliaView further author information
,
Adam McCluskeyDepartment of Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia; View further author information
&
Nigel C. JonesDepartment of Medicine, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Australia; ;Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; ;Department of Neurology, The Alfred Hospital, Melbourne, Australia; Correspondence[email protected]
ORCID Iconhttp://orcid.org/0000-0002-1080-8439View further author information
ORCID Icon show all
Pages 144-155 | Received 05 Nov 2018, Accepted 04 Feb 2019, Published online: 25 Mar 2019
 
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Abstract

Glioma stem cells (GSCs) play major roles in drug resistance, tumour maintenance and recurrence of glioblastoma. We investigated inhibition of the GTPase dynamin 2 as a therapy for glioblastoma. Glioma cell lines and patient-derived GSCs were treated with dynamin inhibitors, Dynole 34-2 and CyDyn 4-36. We studied about cell viability, and GSC neurosphere formation in vitro and orthotopic tumour growth in vivo. Dynamin inhibition reduced glioblastoma cell line viability and suppressed neurosphere formation and migration of GSCs. Tumour growth was reduced by CyDyn 4-36 treatment. Dynamin 2 inhibition therefore represents a novel approach for stem cell-directed Glioblastoma therapy.

Additional information

Funding

This work was supported by The Royal Melbourne Hospital Neuroscience Foundation, ARC Discovery Project (A.M. and P.J.R.), and NHMRC Project grant (A.M., N.C.J. and P.J.R.).

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