The crucial role of cancer stem cells (CSCs) in the pathology of malignant diseases has been extensively studied during the last decade. Nestin, a class VI intermediate filament protein, was originally detected in neural stem cells during development. Its expression has also been reported in different tissues under various pathological conditions. Specifically, nestin has been shown to be expressed in transformed cells of various human malignancies, and a correlation between its expression and the clinical course of some diseases has been proved. Furthermore, the coexpression of nestin with other stem cell markers was described as a CSC phenotype that was subsequently verified using tumorigenicity assays. The primary aim of this review is to summarize the recent findings regarding nestin expression in CSCs, its possible role in CSC phenotypes, particularly with respect to capacity for self-renewal, and its utility as a putative marker of CSCs.
- Keywords
- Cancer stem cells, cytoskeleton, intermediate filaments, nestin, tumor markers,
- MeSH
- Humans MeSH
- Biomarkers, Tumor metabolism MeSH
- Neoplastic Stem Cells metabolism MeSH
- Neoplasms metabolism pathology MeSH
- Nestin metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Biomarkers, Tumor MeSH
- NES protein, human MeSH Browser
- Nestin MeSH
Nestin is a class VI intermediate filament protein expressed in the cytoplasm of stem and progenitor cells in the mammalian CNS during development. In adults, nestin is present only in a small subset of cells and tissues, including the subventricular zone of the adult mammalian brain, where neurogenesis occurs. Nestin expression has also been detected under such pathological conditions as ischemia, inflammation, and brain injury, as well as in various types of human solid tumors and their corresponding cell lines. Furthermore, nestin was recently found in the nuclei of glioblastoma, neuroblastoma, and angiosarcoma cells and it was proved to interact directly with the nuclear DNA in neuroblastoma cells. Here, we perform the first study of the intracellular distribution of nestin in cell lines derived from neurogenic tumors. Using immunodetection methods, we examined nestin expression in tumor-derived cell lines obtained from 11 patients with neuroblastoma, medulloblastoma, or glioblastoma multiforme. Besides its standard cytoplasmic localization, nestin was present in the nuclei of two neuroblastoma cell lines and one medulloblastoma cell line. Nestin was only present in the nuclei of cells with diffuse cytoplasmic staining for this protein, and the proportion of cells positive for nestin in nuclei, as well as the intensity of staining, varied. The presence of nestin in the nuclei was confirmed by both transmission electron microscopy and Western blotting. Our results indicate that the presence of nestin in the nuclei of tumor cells is not very rare, especially under in vitro conditions.
- MeSH
- Cell Nucleus chemistry metabolism ultrastructure MeSH
- Child MeSH
- Fluorescent Antibody Technique MeSH
- Glioblastoma metabolism ultrastructure MeSH
- Immunohistochemistry MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Medulloblastoma metabolism ultrastructure MeSH
- Cell Line, Tumor MeSH
- Nestin MeSH
- Neuroblastoma metabolism ultrastructure MeSH
- Child, Preschool MeSH
- Intermediate Filament Proteins analysis metabolism MeSH
- Nerve Tissue Proteins analysis metabolism MeSH
- Aged MeSH
- Microscopy, Electron, Transmission MeSH
- Blotting, Western MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- NES protein, human MeSH Browser
- Nestin MeSH
- Intermediate Filament Proteins MeSH
- Nerve Tissue Proteins MeSH