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01-07-2010 | Original Paper

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

Authors: 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

Published in: Child's Nervous System | Issue 7/2010

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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Title: Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity
Authors: 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
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Child's Nervous System / Issue 7/2010
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-010-1087-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Objects

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objects

Methods

Results

Conclusions

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