BACKGROUND: The vascular niche necessary for cancer stem cell maintenance is a potential target for cancer therapy. MATERIALS AND METHODS: Human glioma xenografts were treated with IFN-β delivered systemically via a liver-targeted, adeno-associated viral vector. The vascular niche was examined with immunofluorescence for glioma stem cells, endothelial cells, and perivascular cells. RESULTS: Although IFN-β was not directly toxic to glioma stem cells in vitro, IFN-β decreased tumor size and the number of stem cells recovered in both heterotopic and orthotopic models. Treatment with IFN-β increased perivascular cells investing the tumor vasculature (6-fold) distancing stem cells from endothelial cells. Additionally, vascular smooth muscle cells co-cultured between stem cells and endothelial cells decreased stem cell recovery. CONCLUSION: Continuous delivery of IFN-β decreased the number of stem cells in glioma xenografts by disrupting the vascular niche through an increase in perivascular cells, which created a barrier between the glioma stem cells and the endothelial cells.
BACKGROUND: The vascular niche necessary for cancer stem cell maintenance is a potential target for cancer therapy. MATERIALS AND METHODS:Humanglioma xenografts were treated with IFN-β delivered systemically via a liver-targeted, adeno-associated viral vector. The vascular niche was examined with immunofluorescence for glioma stem cells, endothelial cells, and perivascular cells. RESULTS: Although IFN-β was not directly toxic to glioma stem cells in vitro, IFN-β decreased tumor size and the number of stem cells recovered in both heterotopic and orthotopic models. Treatment with IFN-β increased perivascular cells investing the tumor vasculature (6-fold) distancing stem cells from endothelial cells. Additionally, vascular smooth muscle cells co-cultured between stem cells and endothelial cells decreased stem cell recovery. CONCLUSION: Continuous delivery of IFN-β decreased the number of stem cells in glioma xenografts by disrupting the vascular niche through an increase in perivascular cells, which created a barrier between the glioma stem cells and the endothelial cells.
Authors: Jason W Denbo; Regan F Williams; W Shannon Orr; Thomas L Sims; Catherine Y Ng; Junfang Zhou; Yunyu Spence; Christopher L Morton; Amit C Nathwani; Christopher Duntsch; Lawrence M Pfeffer; Andrew M Davidoff Journal: Surgery Date: 2011-09 Impact factor: 3.982
Authors: Gina Li; Nicolas Bonamici; Mahua Dey; Maciej S Lesniak; Irina V Balyasnikova Journal: Expert Opin Drug Deliv Date: 2017-09-18 Impact factor: 6.648
Authors: Stuart J Smith; Hanna Tilly; Jennifer H Ward; Donald C Macarthur; James Lowe; Beth Coyle; Richard G Grundy Journal: Acta Neuropathol Date: 2012-02-07 Impact factor: 17.088
Authors: Nevenka Dudvarski Stankovic; Nicola Hoppmann; Marcin Teodorczyk; Ella L Kim; Matthias Bros; Alf Giese; Frauke Zipp; Mirko H H Schmidt Journal: Oncotarget Date: 2016-12-27
Authors: Fabian Wolpert; Caroline Happold; Guido Reifenberger; Ana-Maria Florea; René Deenen; Patrick Roth; Marian Christoph Neidert; Katrin Lamszus; Manfred Westphal; Michael Weller; Günter Eisele Journal: PLoS One Date: 2015-10-06 Impact factor: 3.240