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

19 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Angiostatins
Oncolytic Viruses
Endostatins
Glioma
Stem Cells
Gene Expression
Genes
Gene Fusion
Neural Stem Cells
Neoplastic Stem Cells
Genetic Therapy
Endothelial Cells
Stem Cell Niche
In Vitro Techniques
Nestin
Brain
Blood Vessels
Suspensions
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

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

Cite this

Glioma stem cells targeted by oncolytic virus carrying endostatin- angiostatin fusion gene and the expression of its exogenous gene in vitro. / Zhu, Guidong; Su, Wei; Jin, Guishan; Xu, Fujian; Hao, Shuyu; Guan, Fangxia; Jia, William; Liu, Fusheng.

In: Brain Research, Vol. 1390, 16.05.2011, p. 59-69.

Research output: Contribution to journalArticle

Zhu, Guidong ; Su, Wei ; Jin, Guishan ; Xu, Fujian ; Hao, Shuyu ; Guan, Fangxia ; Jia, William ; Liu, Fusheng. / Glioma stem cells targeted by oncolytic virus carrying endostatin- angiostatin fusion gene and the expression of its exogenous gene in vitro. In: Brain Research. 2011 ; Vol. 1390. pp. 59-69.
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