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Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties...

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Autores principales: Liu, Qinghai, Nguyen, David H., Dong, Qinghua, Shitaku, Peter, Chung, Kenneth, Liu, On Ying, Tso, Jonathan L., Liu, Jason Y., Konkankit, Veerauo, Cloughesy, Timothy F., Mischel, Paul S., Lane, Timothy F., Liau, Linda M., Nelson, Stanley F., Tso, Cho-Lea
Formato: Texto
Lenguaje:English
Publicado: Springer US 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705704/
https://www.ncbi.nlm.nih.gov/pubmed/19468690
http://dx.doi.org/10.1007/s11060-009-9919-z
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author Liu, Qinghai
Nguyen, David H.
Dong, Qinghua
Shitaku, Peter
Chung, Kenneth
Liu, On Ying
Tso, Jonathan L.
Liu, Jason Y.
Konkankit, Veerauo
Cloughesy, Timothy F.
Mischel, Paul S.
Lane, Timothy F.
Liau, Linda M.
Nelson, Stanley F.
Tso, Cho-Lea
author_facet Liu, Qinghai
Nguyen, David H.
Dong, Qinghua
Shitaku, Peter
Chung, Kenneth
Liu, On Ying
Tso, Jonathan L.
Liu, Jason Y.
Konkankit, Veerauo
Cloughesy, Timothy F.
Mischel, Paul S.
Lane, Timothy F.
Liau, Linda M.
Nelson, Stanley F.
Tso, Cho-Lea
author_sort Liu, Qinghai
collection PubMed
description Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11060-009-9919-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-27057042009-07-07 Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors Liu, Qinghai Nguyen, David H. Dong, Qinghua Shitaku, Peter Chung, Kenneth Liu, On Ying Tso, Jonathan L. Liu, Jason Y. Konkankit, Veerauo Cloughesy, Timothy F. Mischel, Paul S. Lane, Timothy F. Liau, Linda M. Nelson, Stanley F. Tso, Cho-Lea J Neurooncol Priority Report Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11060-009-9919-z) contains supplementary material, which is available to authorized users. Springer US 2009-05-26 2009-08 /pmc/articles/PMC2705704/ /pubmed/19468690 http://dx.doi.org/10.1007/s11060-009-9919-z Text en © The Author(s) 2009
spellingShingle Priority Report
Liu, Qinghai
Nguyen, David H.
Dong, Qinghua
Shitaku, Peter
Chung, Kenneth
Liu, On Ying
Tso, Jonathan L.
Liu, Jason Y.
Konkankit, Veerauo
Cloughesy, Timothy F.
Mischel, Paul S.
Lane, Timothy F.
Liau, Linda M.
Nelson, Stanley F.
Tso, Cho-Lea
Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
title Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
title_full Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
title_fullStr Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
title_full_unstemmed Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
title_short Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
title_sort molecular properties of cd133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors
topic Priority Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705704/
https://www.ncbi.nlm.nih.gov/pubmed/19468690
http://dx.doi.org/10.1007/s11060-009-9919-z
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