1. Podocalyxin-like protein is expressed in glioblastoma multiforme stem-like cells and is associated with poor outcome.
- Author
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Binder ZA, Siu 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, and Gallia GL
- Subjects
- Adult, Biomarkers, Tumor metabolism, Brain Neoplasms metabolism, Brain Neoplasms mortality, Brain Neoplasms pathology, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Flow Cytometry, Gene Knockdown Techniques, Glioblastoma metabolism, Glioblastoma mortality, Glioblastoma pathology, Humans, Neoplasm Grading, Neoplastic Stem Cells pathology, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Polycomb Repressive Complex 1 genetics, Polycomb Repressive Complex 1 metabolism, Prognosis, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, Sialoglycoproteins metabolism, Spheroids, Cellular metabolism, Spheroids, Cellular pathology, Survival Analysis, Biomarkers, Tumor genetics, Brain Neoplasms genetics, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Neoplastic Stem Cells metabolism, Sialoglycoproteins genetics
- 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.
- Published
- 2013
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