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

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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 parental MB 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.

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Acknowledgement

This study was supported by research grants from the National Science Council (NSC-97-3111-B-075-001-MY3, 97-2314-B-075-056-MY3), Taipei Veterans General Hospital (V97E1-008, V97F-001), Yen-Tjing-Ling Medical Foundation, Taipei City Hospital (96001-62-014, 96001-62-018, 96002-62-092), and National Yang-Ming University (Ministry of Education, Aim for the Top University Plan), Taiwan.

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Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Cheng-Chia Yu & Hung-Hai Ku

  2. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Guang-Yuh Chiou, Yi-Yen Lee, Pin-I Huang, Yi-Wei Cheng & Lung-Kuo Tai

  3. Institute of Pharmacy, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Yuh-Lih Chang & Shih-Hwa Chiou

  4. Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan

    Pin-I Huang & Yi-Wei Cheng

  5. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

    Guang-Yuh Chiou, Yuh-Lih Chang, Lung-Kuo Tai & Shih-Hwa Chiou

  6. Division of Pediatric Neurosurgery, The Neurological Institute, Taipei Veterans General Hospital, No. 201 Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan

    Yi-Yen Lee & Tai-Tong Wong

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  1. Cheng-Chia Yu
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Corresponding authors

Correspondence to Shih-Hwa Chiou or Tai-Tong Wong.

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Yu, Chiou, and Lee contributed equally.

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Yu, CC., Chiou, GY., Lee, YY. et al. Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity. Childs Nerv Syst 26, 897–904 (2010). https://doi.org/10.1007/s00381-010-1087-0

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  • DOI: https://doi.org/10.1007/s00381-010-1087-0

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