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Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor and is associated with poor survival. Recently, stem-like cell populations have been identified in numerous malignancies including GBM. To identify genes whose expression is changed with differentiation, we compared...

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Autores principales: Binder, Zev A., Siu, I-Mei, Eberhart, Charles G., ap Rhys, Colette, Bai, Ren-Yuan, Staedtke, Verena, Zhang, Hao, Smoll, Nicolas R., Piantadosi, Steven, Piccirillo, Sara G., DiMeco, Francesco, Weingart, Jon D., Vescovi, Angelo, Olivi, Alessandro, Riggins, Gregory J., Gallia, Gary L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797817/
https://www.ncbi.nlm.nih.gov/pubmed/24146797
http://dx.doi.org/10.1371/journal.pone.0075945
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author Binder, Zev A.
Siu, I-Mei
Eberhart, Charles G.
ap Rhys, Colette
Bai, Ren-Yuan
Staedtke, Verena
Zhang, Hao
Smoll, Nicolas R.
Piantadosi, Steven
Piccirillo, Sara G.
DiMeco, Francesco
Weingart, Jon D.
Vescovi, Angelo
Olivi, Alessandro
Riggins, Gregory J.
Gallia, Gary L.
author_facet Binder, Zev A.
Siu, I-Mei
Eberhart, Charles G.
ap Rhys, Colette
Bai, Ren-Yuan
Staedtke, Verena
Zhang, Hao
Smoll, Nicolas R.
Piantadosi, Steven
Piccirillo, Sara G.
DiMeco, Francesco
Weingart, Jon D.
Vescovi, Angelo
Olivi, Alessandro
Riggins, Gregory J.
Gallia, Gary L.
author_sort Binder, Zev A.
collection PubMed
description Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor and is associated with poor survival. Recently, stem-like cell populations have been identified in numerous malignancies including GBM. To identify genes whose expression is changed with differentiation, we compared transcript profiles from a GBM oncosphere line before and after differentiation. Bioinformatic analysis of the gene expression profiles identified podocalyxin-like protein (PODXL), a protein highly expressed in human embryonic stem cells, as a potential marker of undifferentiated GBM stem-like cells. The loss of PODXL expression upon differentiation of GBM stem-like cell lines was confirmed by quantitative real-time PCR and flow cytometry. Analytical flow cytometry of numerous GBM oncosphere lines demonstrated PODXL expression in all lines examined. Knockdown studies and flow cytometric cell sorting experiments demonstrated that PODXL is involved in GBM stem-like cell proliferation and oncosphere formation. Compared to PODXL-negative cells, PODXL-positive cells had increased expression of the progenitor/stem cell markers Musashi1, SOX2, and BMI1. Finally, PODXL expression directly correlated with increasing glioma grade and was a marker for poor outcome in patients with GBM. In summary, we have demonstrated that PODXL is expressed in GBM stem-like cells and is involved in cell proliferation and oncosphere formation. Moreover, high PODXL expression correlates with increasing glioma grade and decreased overall survival in patients with GBM.
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spelling pubmed-37978172013-10-21 Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome Binder, Zev A. Siu, I-Mei Eberhart, Charles G. ap Rhys, Colette Bai, Ren-Yuan Staedtke, Verena Zhang, Hao Smoll, Nicolas R. Piantadosi, Steven Piccirillo, Sara G. DiMeco, Francesco Weingart, Jon D. Vescovi, Angelo Olivi, Alessandro Riggins, Gregory J. Gallia, Gary L. PLoS One Research Article Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor and is associated with poor survival. Recently, stem-like cell populations have been identified in numerous malignancies including GBM. To identify genes whose expression is changed with differentiation, we compared transcript profiles from a GBM oncosphere line before and after differentiation. Bioinformatic analysis of the gene expression profiles identified podocalyxin-like protein (PODXL), a protein highly expressed in human embryonic stem cells, as a potential marker of undifferentiated GBM stem-like cells. The loss of PODXL expression upon differentiation of GBM stem-like cell lines was confirmed by quantitative real-time PCR and flow cytometry. Analytical flow cytometry of numerous GBM oncosphere lines demonstrated PODXL expression in all lines examined. Knockdown studies and flow cytometric cell sorting experiments demonstrated that PODXL is involved in GBM stem-like cell proliferation and oncosphere formation. Compared to PODXL-negative cells, PODXL-positive cells had increased expression of the progenitor/stem cell markers Musashi1, SOX2, and BMI1. Finally, PODXL expression directly correlated with increasing glioma grade and was a marker for poor outcome in patients with GBM. In summary, we have demonstrated that PODXL is expressed in GBM stem-like cells and is involved in cell proliferation and oncosphere formation. Moreover, high PODXL expression correlates with increasing glioma grade and decreased overall survival in patients with GBM. Public Library of Science 2013-10-16 /pmc/articles/PMC3797817/ /pubmed/24146797 http://dx.doi.org/10.1371/journal.pone.0075945 Text en © 2013 Binder et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Binder, Zev A.
Siu, I-Mei
Eberhart, Charles G.
ap Rhys, Colette
Bai, Ren-Yuan
Staedtke, Verena
Zhang, Hao
Smoll, Nicolas R.
Piantadosi, Steven
Piccirillo, Sara G.
DiMeco, Francesco
Weingart, Jon D.
Vescovi, Angelo
Olivi, Alessandro
Riggins, Gregory J.
Gallia, Gary L.
Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome
title Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome
title_full Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome
title_fullStr Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome
title_full_unstemmed Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome
title_short Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome
title_sort podocalyxin-like protein is expressed in glioblastoma multiforme stem-like cells and is associated with poor outcome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797817/
https://www.ncbi.nlm.nih.gov/pubmed/24146797
http://dx.doi.org/10.1371/journal.pone.0075945
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