Targeting Glioma Stem Cells by Functional Inhibition of Dynamin 2: A Novel Treatment Strategy for Glioblastoma
Rodney Luwor, Andrew P Morokoff, Stephanie Amiridis, Giovanna D'Abaco, Lucia Paradiso, Stanley S Stylli, Hong PT Nguyen, Mark Tarleton, Kelly A Young, Terence J O'Brien, Phillip J Robinson, Megan Chircop, Adam McCluskey, Nigel C Jones
CANCER INVESTIGATION | TAYLOR & FRANCIS INC | Published : 2019
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.
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.).