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

Zev A. Binder, I. Mei SiuI-Mei, Charles G. Eberhart, Colette ap Rhys, Ren Yuan Bai, Verena Staedtke, Hao Zhang, Nicolas R. Smoll, Steven Piantadosi, Sara G. Piccirillo, Francesco DiMeco, Jon D. Weingart, Angelo Vescovi, Alessandro Olivi, Gregory J. Riggins, Gary L. Gallia

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere75945
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 16 2013

Fingerprint

Glioblastoma
oncospheres
Stem Cells
stems
protein synthesis
Proteins
proteins
cells
Cells
flow cytometry
stem cells
cell proliferation
Flow cytometry
Cell proliferation
gene expression
Stem cells
Gene expression
Glioma
embryonic stem cells
Flow Cytometry

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Binder, Z. A., SiuI-Mei, I. M., Eberhart, C. G., ap Rhys, C., Bai, R. Y., Staedtke, V., ... Gallia, G. L. (2013). Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome. PLoS One, 8(10), [e75945]. https://doi.org/10.1371/journal.pone.0075945

Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome. / Binder, Zev A.; SiuI-Mei, 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.

In: PLoS One, Vol. 8, No. 10, e75945, 16.10.2013.

Research output: Contribution to journalArticle

Binder, ZA, SiuI-Mei, IM, Eberhart, CG, ap Rhys, C, Bai, RY, Staedtke, V, Zhang, H, Smoll, NR, Piantadosi, S, Piccirillo, SG, DiMeco, F, Weingart, JD, Vescovi, A, Olivi, A, Riggins, GJ & Gallia, GL 2013, 'Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome', PLoS One, vol. 8, no. 10, e75945. https://doi.org/10.1371/journal.pone.0075945
Binder, Zev A. ; SiuI-Mei, 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. In: PLoS One. 2013 ; Vol. 8, No. 10.
@article{885c8d5722c64734be27ea328045ea87,
title = "Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome",
abstract = "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.",
author = "Binder, {Zev A.} and SiuI-Mei, {I. Mei} and Eberhart, {Charles G.} and {ap Rhys}, Colette and Bai, {Ren Yuan} and Verena Staedtke and Hao Zhang and Smoll, {Nicolas R.} and Steven Piantadosi and Piccirillo, {Sara G.} and Francesco DiMeco and Weingart, {Jon D.} and Angelo Vescovi and Alessandro Olivi and Riggins, {Gregory J.} and Gallia, {Gary L.}",
year = "2013",
month = "10",
day = "16",
doi = "10.1371/journal.pone.0075945",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome

AU - Binder, Zev A.

AU - SiuI-Mei, I. Mei

AU - Eberhart, Charles G.

AU - ap Rhys, Colette

AU - Bai, Ren Yuan

AU - Staedtke, Verena

AU - Zhang, Hao

AU - Smoll, Nicolas R.

AU - Piantadosi, Steven

AU - Piccirillo, Sara G.

AU - DiMeco, Francesco

AU - Weingart, Jon D.

AU - Vescovi, Angelo

AU - Olivi, Alessandro

AU - Riggins, Gregory J.

AU - Gallia, Gary L.

PY - 2013/10/16

Y1 - 2013/10/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84885706290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885706290&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0075945

DO - 10.1371/journal.pone.0075945

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e75945

ER -