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

doi:10.1007/s00381-010-1087-0

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

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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 language	English
Pages (from-to)	897-904
Number of pages	8
Journal	Child's Nervous System
Volume	26
Issue number	7
DOIs	https://doi.org/10.1007/s00381-010-1087-0
Publication status	Published - Jul 2010
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Clinical Neurology

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10.1007/s00381-010-1087-0

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@article{8c1dd799033049348ada54bd8b1a03b2,

title = "Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity",

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.",

keywords = "Medulloblastoma (MB), Radiosensitivity, TNF-related apoptosis-inducing ligand (TRAIL), Tumor stem-like cells (TSC)",

author = "Yu, {Cheng Chia} and Chiou, {Guang Yuh} and Lee, {Yi Yen} and Chang, {Yuh Lih} and Huang, {Pin I.} and Cheng, {Yi Wei} and Tai, {Lung Kuo} and Ku, {Hung Hai} and Chiou, {Shih Hwa} and Wong, {Tai Tong}",

note = "Funding Information: 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.",

year = "2010",

month = jul,

doi = "10.1007/s00381-010-1087-0",

language = "English",

volume = "26",

pages = "897--904",

journal = "Child's Nervous System",

issn = "0256-7040",

publisher = "Springer Verlag",

number = "7",

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TY - JOUR

T1 - Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity

AU - Yu, Cheng Chia

AU - Chiou, Guang Yuh

AU - Lee, Yi Yen

AU - Chang, Yuh Lih

AU - Huang, Pin I.

AU - Cheng, Yi Wei

AU - Tai, Lung Kuo

AU - Ku, Hung Hai

AU - Chiou, Shih Hwa

AU - Wong, Tai Tong

N1 - Funding Information: 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.

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

KW - Medulloblastoma (MB)

KW - Radiosensitivity

KW - TNF-related apoptosis-inducing ligand (TRAIL)

KW - Tumor stem-like cells (TSC)

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JO - Child's Nervous System

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

Abstract

Keywords

ASJC Scopus subject areas

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