Podocalyxin-like protein is expressed in glioblastoma multiforme stem-like cells and is associated with poor outcome
Autor: | Charles G. Eberhart, Sara Grazia Maria Piccirillo, Gregory J. Riggins, Renyuan Bai, Zev A. Binder, Nicolas R. Smoll, Angelo L. Vescovi, Francesco DiMeco, Steven Piantadosi, I-Mei Siu, Alessandro Olivi, Jon D. Weingart, Gary L. Gallia, Colette M. Ap Rhys, Hao Zhang, Verena Staedtke |
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Přispěvatelé: | Harrison, Jeffrey K, Binder, Z, Siu, I, Eberhart, C, Ap Rhys, C, Bai, R, Staedtke, V, Zhang, H, Smoll, N, Piantadosi, S, Piccirillo, S, Dimeco, F, Weingart, J, Vescovi, A, Olivi, A, Riggins, G, Gallia, G |
Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Cellular pathology
Pathology Cellular differentiation lcsh:Medicine Stem cell marker 0302 clinical medicine Stem Cell Research - Nonembryonic - Human lcsh:Science Cancer Polycomb Repressive Complex 1 0303 health sciences Multidisciplinary Tumor Brain Neoplasms RNA-Binding Proteins Cell Differentiation Cell sorting Prognosis Flow Cytometry Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Gene Knockdown Techniques Neoplastic Stem Cells Stem Cell Research - Nonembryonic - Non-Human Research Article Adult medicine.medical_specialty General Science & Technology Sialoglycoproteins Nerve Tissue Proteins Biology Cell Line glioblastoma multiforme 03 medical and health sciences Rare Diseases SOX2 Cell Line Tumor Spheroids Cellular Glioma Biomarkers Tumor medicine Genetics Humans 030304 developmental biology Cell Proliferation Neoplastic SOXB1 Transcription Factors lcsh:R Neurosciences medicine.disease Stem Cell Research Embryonic stem cell Survival Analysis Brain Disorders nervous system diseases Brain Cancer Gene Expression Regulation BMI1 Cancer research lcsh:Q Cellular Spheroids Neoplasm Grading Glioblastoma Biomarkers |
Zdroj: | PLoS ONE, Vol 8, Iss 10, p e75945 (2013) PloS one, vol 8, iss 10 PLoS ONE Binder, ZA; SiuI-Mei, IM; Eberhart, CG; ap Rhys, C; Bai, RY; Staedtke, V; et al.(2013). Podocalyxin-Like Protein Is Expressed in Glioblastoma Multiforme Stem-Like Cells and Is Associated with Poor Outcome. PLoS ONE, 8(10). doi: 10.1371/journal.pone.0075945. UCLA: Retrieved from: http://www.escholarship.org/uc/item/9q51d0cb |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0075945. |
Popis: | 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. © 2013 Binder et al. |
Databáze: | OpenAIRE |
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