Glioma stem cells targeted by oncolytic virus carrying endostatin- angiostatin fusion gene and the expression of its exogenous gene in vitro

Guidong Zhu, Wei Su, Guishan Jin, Fujian Xu, Shuyu Hao, Fangxia Guan, William Jia, Fusheng Liu

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)59-69
Number of pages11
JournalBrain research
Volume1390
DOIs
StatePublished - May 16 2011

Keywords

  • Brain glioma
  • Endostatin-angiostatin
  • Glioma stem cells
  • Virus-gene therapy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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