title: Cell surface Nestin is a biomarker for glioma stem cells.
abstract: Cancer stem cells (CSCs) are the most aggressive cell type in many malignancies. Cell surface proteins are generally used to isolate and characterize CSCs. Therefore, the identification of CSC-specific cell surface markers is very important for the diagnosis and treatment of malignancies. We found that Nestin (a type VI intermediate filament protein), like the glioma stem cell (GSC) markers CD133 and CD15, exhibited different levels of expression in primary human glioblastoma specimens. Similar to our previous finding that cytoplasmic Nestin is expressed as a cell surface form in mouse GSCs, the cell surface form of Nestin was also expressed at different levels in human GSCs. We isolated cell surface Nestin-positive cell populations from human GSCs by fluorescence-activated cell sorting FACS analysis, and observed that these populations exhibited robust CSC properties, such as increased tumorsphere-forming ability and tumorsphere size. Mechanistically, we found that DAPT, a γ-secretase (a multi-subunit protease complex) inhibitor, reduced the proportion of cell surface Nestin-positive cells in human GSCs in a time- and dose-dependent manner, without significant changes in total Nestin expression, implying that a post-translational modification was involved in the generation of cell surface Nestin. Taken together, our data provides the first evidence that cell surface Nestin may serve as a promising GSC marker for the isolation and characterization of heterogeneous GSCs in glioblastomas.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Xiong
authors.initials: X
authors.lastname: Jin
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Jung
authors.forename: Samuel
authors.initials: S
authors.lastname: Beck
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D000071916:AC133 Antigen; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005647:Fucosyltransferases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D016256:Lewis X Antigen / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D010455:Peptides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015203:Reproducibility of Results; D059010:Single-Cell Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; D016256:Lewis X Antigen; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C066693:FUT4 protein, human; D005647:Fucosyltransferases; D053829:Amyloid Precursor Protein Secretases