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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Published in | PloS one Vol. 8; no. 10; p. e75945 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
16.10.2013
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: ZAB IS GJR GLG. Performed the experiments: ZAB IS RYB VS HZ GLG. Analyzed the data: ZAB IS CGE NRS SP GJR GLG. Contributed reagents/materials/analysis tools: ZAB CR SGP FD JDW AV AO GLG. Wrote the paper: ZAB IS GLG. Current address: Cedars Sinai Medical Center, Los Angeles, California, United States of America Competing Interests: The authors have declared that no competing interests exist. Current address: Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0075945 |