title: Podocalyxin-like protein is expressed in glioblastoma multiforme stem-like cells and is associated with poor outcome.
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.
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America ; Johns Hopkins Physical Science Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Binder
authors.forename: I-Mei
authors.initials: IM
authors.lastname: Siu
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.forename: Colette
authors.initials: C
authors.lastname: Ap Rhys
authors.forename: Ren-Yuan
authors.initials: RY
authors.lastname: Bai
authors.forename: Verena
authors.initials: V
authors.lastname: Staedtke
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Nicolas R
authors.initials: NR
authors.lastname: Smoll
authors.forename: Steven
authors.initials: S
authors.lastname: Piantadosi
authors.forename: Sara G
authors.initials: SG
authors.lastname: Piccirillo
authors.forename: Francesco
authors.initials: F
authors.lastname: Dimeco
authors.forename: Jon D
authors.initials: JD
authors.lastname: Weingart
authors.forename: Angelo
authors.initials: A
authors.lastname: Vescovi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Olivi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D012795:Sialoglycoproteins; C001643:podocalyxin; D063150:Polycomb Repressive Complex 1