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
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