Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity

Cheng Chia Yu, Guang-Yuh Chiou, Yi Yen Lee, Yuh Lih Chang, Pin I. Huang, Yi Wei Cheng, Lung Kuo Tai, Hung Hai Ku, Shih Hwa Chiou*, Tai Tong Wong

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Objects Medulloblastoma (MB) is the most malignant primary brain tumor in early childhood that contains cellular and functional heterogeneity. Recent evidence has demonstrated that the tumor stem cells (TSC) may explain the radiochemoresistance of brain tumors, including MB. The aim of the present study is to investigate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) in viability and tumorigenicity of MB cells and MB-derived TSC. Methods MB-associated TSC were isolated and cultured by serum-free medium with bFGF and EGF. The parental MB cells and MB-TSC cells were treated with TRAIL in different concentrations and assessed for cell viability, invasion ability, colony forming ability, and radiotherapy effect. Results We enrich a subpopulation of MB-TSC cells using tumor spheroid formation approach. MB-TSC display enhanced self-renewal and highly expressed -stemness- genes (CD133, Sox-2, Bmi1, Nestin). Additionally,MB-TSC showed significant resistance to TRAIL-induced apoptosis and radiosensitivity compared to the parentalMB cells due antiapoptotic gene (c-FLIP, Caspase 8, Bcl-2, and Bax) upregulation. Conclusions Our data suggest that MB-TSC are resistant to TRAIL-induced apoptosis and tumorigenic properties. Understanding the molecular mechanisms by which to operate the physiological characteristics in MB-TSC cells offers attractive approach for MB treatment.

Original languageEnglish
Pages (from-to)897-904
Number of pages8
JournalChild's Nervous System
Volume26
Issue number7
DOIs
StatePublished - 1 Jul 2010

Keywords

  • Medulloblastoma (MB)
  • Radiosensitivity
  • TNF-related apoptosis-inducing ligand (TRAIL)
  • Tumor stem-like cells (TSC)

Fingerprint Dive into the research topics of 'Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity'. Together they form a unique fingerprint.

  • Cite this

    Yu, C. C., Chiou, G-Y., Lee, Y. Y., Chang, Y. L., Huang, P. I., Cheng, Y. W., Tai, L. K., Ku, H. H., Chiou, S. H., & Wong, T. T. (2010). Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity. Child's Nervous System, 26(7), 897-904. https://doi.org/10.1007/s00381-010-1087-0