Nejvíce citovaný článek - PubMed ID 15677549
Background: The intermediate filament nestin was first described in stem and progenitor cells of neural and mesenchymal origin. Additionally, it is expressed in endothelial cells during wound healing and tumorigenesis. Thus, nestin is widely regarded as a marker for proliferative endothelium. However, little is known about its role in lymphatic endothelium. Methods: Here, we analyzed the expression of nestin in the endothelium of ten human haemangiomas and ten lymphangiomas in situ by immunohistochemistry. This study aimed to investigate the expression of nestin in haemangiomas and lymphangiomas to determine its potential role as a vascular marker. Specifically, we aimed to assess whether nestin expression is restricted to proliferating endothelial cells or also present in non-proliferative blood vessels. Results: Immunohistochemically, haemangiomas were positive for CD31 but negative for D2-40. The endothelial cells within these lesions showed a homogeneous expression of nestin. In contrast, the endothelium of lymphangiomas reacted positively for D2-40 and CD31 but did not show any nestin expression. Additionally, only a few endothelial cells of capillary haemangiomas showed a Ki-67 positivity. Conclusions: The differential expression of nestin in haemangiomas and lymphangiomas indicates a specificity of nestin for the endothelium of blood vessels. The Ki-67 negativity in the majority of the endothelial cells reveals the proliferative quiescence of these cells. These findings indicate that nestin could be used as a marker to differentiate between blood and lymphatic vessels.
- Klíčová slova
- CD31, D2-40, endothelial cells, haemangioma, histology, immunohistochemistry, lymphangioma, nestin,
- Publikační typ
- časopisecké články MeSH
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.
- Klíčová slova
- Cancer stem cells, cytoskeleton, intermediate filaments, nestin, tumor markers,
- MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové kmenové buňky metabolismus MeSH
- nádory metabolismus patologie MeSH
- nestin metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
- NES protein, human MeSH Prohlížeč
- nestin MeSH
Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups--pT1 (35), pT2 (17), pT3 (18) and pT4 (12)--and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries.
- MeSH
- antigeny Thy-1 metabolismus MeSH
- dospělí MeSH
- forkhead transkripční faktory metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- melanom krevní zásobení imunologie patologie MeSH
- mikrocévy metabolismus patofyziologie MeSH
- nádory kůže krevní zásobení imunologie patologie MeSH
- patologická angiogeneze imunologie patologie MeSH
- regulační T-lymfocyty imunologie metabolismus MeSH
- senioři MeSH
- tumor infiltrující lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny Thy-1 MeSH
- forkhead transkripční faktory MeSH
- FOXP3 protein, human MeSH Prohlížeč
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
- buněčné jádro chemie metabolismus ultrastruktura MeSH
- dítě MeSH
- fluorescenční protilátková technika MeSH
- glioblastom metabolismus ultrastruktura MeSH
- imunohistochemie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- meduloblastom metabolismus ultrastruktura MeSH
- nádorové buněčné linie MeSH
- nestin MeSH
- neuroblastom metabolismus ultrastruktura MeSH
- předškolní dítě MeSH
- proteiny intermediálních filament analýza metabolismus MeSH
- proteiny nervové tkáně analýza metabolismus MeSH
- senioři MeSH
- transmisní elektronová mikroskopie MeSH
- western blotting MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- NES protein, human MeSH Prohlížeč
- nestin MeSH
- proteiny intermediálních filament MeSH
- proteiny nervové tkáně MeSH
BACKGROUND: Nestin was originally identified as a class VI intermediate filament protein that is expressed in stem cells and progenitor cells in the mammalian CNS during development. This protein is replaced in the adult organism by other intermediate filament proteins; however, nestin may be re-expressed under certain pathological conditions such as ischemia, inflammation, brain injury, and neoplastic transformation. Nestin has been detected in many kinds of tumors, especially in tumors derived from the CNS. Co-expression of nestin and the CD133 surface molecule is considered to be a marker for cancer stem cells in neurogenic tumors. Our work was aimed at a detailed study of nestin expression in osteosarcomas and osteosarcoma-derived cell lines. METHODS: Using immunodetection methods, we examined nestin in tumor tissue samples from 18 patients with osteosarcomas. We also successfully established permanent cell lines from the tumor tissue of 4 patients and immunodetection of nestin and CD133 was performed on these cell lines. RESULTS: Nestin-positive tumor cells were immunohistochemically detected in all of the examined osteosarcomas, but the proportion of these cells that were positively stained as well as the intensity of staining varied. Nestin-positive cells were rarely observed in 2 tumor samples, and the remaining 16 tumor samples showed various nestin expression patterns ranging from very sporadic occurrence to an overwhelming proportion of cells with strong positive staining. Three of the established osteosarcoma cell lines were demonstrated to be nestin-positive, and only one cell line showed no expression of nestin; this finding corresponds with the rare occurrence of nestin-positive cells in the respective tumor sample. Moreover, three of these osteosarcoma cell lines were undoubtedly proven to be Nes+/CD133+. CONCLUSION: Our results represent the first evidence of nestin expression in osteosarcomas and suggest the possible occurrence of cells with a stem-like phenotype in these tumors.
- MeSH
- antigen AC133 MeSH
- CD antigeny biosyntéza genetika MeSH
- dítě MeSH
- dospělí MeSH
- fluorescenční protilátková technika MeSH
- glykoproteiny biosyntéza genetika MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky metabolismus patologie MeSH
- nestin MeSH
- osteosarkom genetika patologie MeSH
- peptidy genetika MeSH
- proteiny intermediálních filament biosyntéza genetika MeSH
- proteiny nervové tkáně biosyntéza genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigen AC133 MeSH
- CD antigeny MeSH
- glykoproteiny MeSH
- NES protein, human MeSH Prohlížeč
- nestin MeSH
- peptidy MeSH
- PROM1 protein, human MeSH Prohlížeč
- proteiny intermediálních filament MeSH
- proteiny nervové tkáně MeSH