Podocalyxin-like protein is expressed in glioblastoma multiforme stem-like cells and is associated with poor outcome

• Published in: PloS one 2013-10, Vol.8 (10), p.e75945-e75945
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brain; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Brain tumors; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cell survival; Chemotherapy; Comparative analysis; Cytometry; Differentiation; Embryo cells; Embryonic stem cells; Flow Cytometry; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genes; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - mortality; Glioblastoma - pathology; Glioblastoma multiforme; Glioblastomas; Glioma; Humans; Medicine; Metastasis; Neoplasm Grading; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurosurgery; Oncology; Patients; Physicians; Polycomb Repressive Complex 1 - genetics; Polycomb Repressive Complex 1 - metabolism; Prognosis; Proteins; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sialoglycoproteins - genetics; Sialoglycoproteins - metabolism; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Stem cells; Studies; Survival; Survival Analysis; Transcription; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075945

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.