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.
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.
Authors: Matilde Todaro; Mileidys Perez Alea; Anna B Di Stefano; Patrizia Cammareri; Louis Vermeulen; Flora Iovino; Claudio Tripodo; Antonio Russo; Gaspare Gulotta; Jan Paul Medema; Giorgio Stassi Journal: Cell Stem Cell Date: 2007-10-11 Impact factor: 24.633
Authors: Dagmar Beier; Jörg Wischhusen; Wolfgang Dietmaier; Peter Hau; Martin Proescholdt; Alexander Brawanski; Ulrich Bogdahn; Christoph P Beier Journal: Brain Pathol Date: 2008-03-26 Impact factor: 6.508
Authors: Luke Piggott; Nader Omidvar; Salvador Martí Pérez; Rhiannon French; Matthias Eberl; Richard W E Clarkson Journal: Breast Cancer Res Date: 2011-09-14 Impact factor: 6.466
Authors: Jason W-L Eng; Thomas A Mace; Rohit Sharma; Danielle Y F Twum; Peng Peng; John F Gibbs; Rosemarie Pitoniak; Chelsey B Reed; Scott I Abrams; Elizabeth A Repasky; Bonnie L Hylander Journal: J Immunother Cancer Date: 2016-06-21 Impact factor: 13.751