Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes

In glioblastoma multiforme (GBM), brain-tumor-initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC...

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Main Authors:	Cusulin, Carlo, Chesnelong, Charles, Bose, Pinaki, Bilenky, Misha, Kopciuk, Karen, Chan, Jennifer A., Cairncross, J. Gregory, Jones, Steven J., Marra, Marco A., Luchman, H. Artee, Weiss, Samuel
Format:	Online
Language:	English
Published:	Elsevier 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618251/

id	pubmed-4618251
recordtype	oai_dc
spelling	pubmed-46182512015-11-24 Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes Cusulin, Carlo Chesnelong, Charles Bose, Pinaki Bilenky, Misha Kopciuk, Karen Chan, Jennifer A. Cairncross, J. Gregory Jones, Steven J. Marra, Marco A. Luchman, H. Artee Weiss, Samuel Report In glioblastoma multiforme (GBM), brain-tumor-initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM. Elsevier 2015-06-18 /pmc/articles/PMC4618251/ /pubmed/26095605 http://dx.doi.org/10.1016/j.stemcr.2015.05.010 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cusulin, Carlo Chesnelong, Charles Bose, Pinaki Bilenky, Misha Kopciuk, Karen Chan, Jennifer A. Cairncross, J. Gregory Jones, Steven J. Marra, Marco A. Luchman, H. Artee Weiss, Samuel
spellingShingle	Cusulin, Carlo Chesnelong, Charles Bose, Pinaki Bilenky, Misha Kopciuk, Karen Chan, Jennifer A. Cairncross, J. Gregory Jones, Steven J. Marra, Marco A. Luchman, H. Artee Weiss, Samuel Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes
author_facet	Cusulin, Carlo Chesnelong, Charles Bose, Pinaki Bilenky, Misha Kopciuk, Karen Chan, Jennifer A. Cairncross, J. Gregory Jones, Steven J. Marra, Marco A. Luchman, H. Artee Weiss, Samuel
author_sort	Cusulin, Carlo
title	Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes
title_short	Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes
title_full	Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes
title_fullStr	Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes
title_full_unstemmed	Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes
title_sort	precursor states of brain tumor initiating cell lines are predictive of survival in xenografts and associated with glioblastoma subtypes
description	In glioblastoma multiforme (GBM), brain-tumor-initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM.
publisher	Elsevier
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618251/
_version_	1613492084195459072

Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes

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