Enhanced cell growth and tumorigenicity of rat glioma cells by stable expression of human CD133 through multiple molecular actions

Kuan Min Fang, Tzu Chien Lin, Ti Chun Chan, Shi Zhang Ma, Bo Cheng Tzou, Wen Ruei Chang, Jun Jen Liu, Shih Hwa Chiou, Chung Shi Yang, Shun Fen Tzeng

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

CD133 (Prominin-1/AC133) is generally treated as a cell surface marker found on multipotent stem cells and tumor stem-like cells, and its biological function remains debated. Genetically modified rat glioma cell lines were generated by lentiviral gene delivery of human CD133 into rat C6 glioma cells (hCD133+-C6) or by infection of C6 cells with control lentivirus (mock-C6). Stable hCD133 expression promoted the self-renewal ability of C6-formed spheres with an increase in the expression of the stemness markers, Bmi-1 and SOX2. Akt phosphorylation, Notch-1 activation, and Notch-1 target gene expression (Hes-1, Hey1 and Hey2) were increased in hCD133+-C6 when compared to mock-C6. The inhibition of Akt phosphorylation, Notch-1 activation, and Hes-1 in hCD133+-C6 cells effectively suppressed their clonogenic ability, indicating that these factors are involved in expanding the growth of hCD133+-C6. An elevated expression of GTPase-activating protein 27 (Arhgap27) was detected in hCD133+-C6. A decline in the invasion of hCD133+-C6 by knockdown of Arhgap27 expression indicated the critical role of Arhgap27 in promoting cell migration of hCD133+-C6. In vivo study further showed that hCD133+-C6 formed aggressive tumors in vivo compared to mock-C6. Exposure of hCD133+-C6 to arsenic trioxide not only reduced Akt phosphorylation, Notch-1 activation and Hes-1 expression in vitro, but also inhibited their tumorigenicity in vivo. The results show that C6 glioma cells with stable hCD133 expression enhanced their stemness properties with increased Notch-1/Hes-1 signaling, Akt activation, and Arhgap27 action, which contribute to increased cell proliferation and migration of hCD133+-C6 in vitro, as well as progressive tumor formation in vivo.

Original languageEnglish
Pages (from-to)1402-1417
Number of pages16
JournalGLIA
Volume61
Issue number9
DOIs
Publication statusPublished - Sep 2013

Keywords

  • Akt
  • Arhgap27
  • Arsenic trioxide
  • Glioma
  • Hes-1
  • Notch

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

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  • Cite this

    Fang, K. M., Lin, T. C., Chan, T. C., Ma, S. Z., Tzou, B. C., Chang, W. R., Liu, J. J., Chiou, S. H., Yang, C. S., & Tzeng, S. F. (2013). Enhanced cell growth and tumorigenicity of rat glioma cells by stable expression of human CD133 through multiple molecular actions. GLIA, 61(9), 1402-1417. https://doi.org/10.1002/glia.22521