title: Glioma stem cells targeted by oncolytic virus carrying endostatin-angiostatin fusion gene and the expression of its exogenous gene in vitro.
abstract: The development of the cancer stem cell (CSCs) niche theory has provided a new target for the treatment of gliomas. Gene therapy using oncolytic viral vectors has shown great potential for the therapeutic targeting of CSCs. To explore whether a viral vector carrying an exogenous Endo-Angio fusion gene (VAE) can infect and kill glioma stem cells (GSCs), as well as inhibit their vascular niche in vitro, we have collected surgical specimens of human high-grade glioma (world health organization, WHO Classes III-VI) from which we isolated and cultured GSCs under conditions originally designed for the selective expansion of neural stem cells. Our results demonstrate the following: (1) Four lines of GSCs (isolated from 20 surgical specimens) could grow in suspension, were multipotent, had the ability to self-renew and expressed the neural stem cell markers, CD133 and nestin. (2) VAE could infect GSCs and significantly inhibit their viability. (3) The Endo-Angio fusion gene was expressed in GSCs 48 h after VAE infection and could inhibit the proliferation of human brain microvascular endothelial cells (HBMEC). (4) Residual viable cells lose the ability of self-renewal and adherent differentiation. In conclusion, VAE can significantly inhibit the activity of GSCs in vitro and the expression of exogenous Endo-Angio fusion gene can inhibit HBMEC proliferation. VAE can be used as a novel virus-gene therapy strategy for glioma.
authors: Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing 100050, P.R. China.
authors: Guidong
authors: G
authors: Zhu
authors: Wei
authors: W
authors: Su
authors: Guishan
authors: G
authors: Jin
authors: Fujian
authors: F
authors: Xu
authors: Shuyu
authors: S
authors: Hao
authors: Fangxia
authors: F
authors: Guan
authors: William
authors: W
authors: Jia
authors: Fusheng
authors: F
authors: Liu
mesh_terms: D043168:Angiostatins / Q000008:administration & dosage / Q000235:genetics*; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D043169:Endostatins / Q000008:administration & dosage / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000008:administration & dosage / Q000235:genetics; D050504:Oncolytic Viruses / Q000235:genetics*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D043169:Endostatins; D015514:Oncogene Proteins, Fusion; D043168:Angiostatins