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.
|Number of pages||6|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 2013 Apr 19|
Bibliographical noteFunding Information:
This work was supported by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1020270) and a Korea University grant. We thank Dr. Akio Soeda for providing the X01, X02, and X03 GSCs, and Dr. Ichiro Nakano for providing the AC17, AC20, 84NS, 528NS, MD13, MD30, and 1123NS GSCs.
- Glioma stem cells
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology