Nestin Dotaz Zobrazit nápovědu
Nestin je jedno z intermediárních filament exprimovaných v proliferujících neuronálních proge- nitorových buňkách CNS a PNS (centrálního a periferního nervového systému). Jeho postnatální reexprese se objevuje zejména u nádorů CNS a koreluje s vysokým stupněm malignity. Naše studie je zaměřena na sledování exprese nestinu u benigních a maligních kožních melanocytárních lézí, s cílem zjistit prognostický význam tohoto proteinu. Vyšetřili jsme 127 bioptických vzorků, z nichž bylo 42 nodulárních melanomů (NM), 32 superficiálních melanomů (SSM), 10 dysplastických névů (DN) a 43 běžných intradermálních i dermoepidermálních pigmentových névů. Prokázali jsme vý- znamné zvýšení exprese nestinu u jednotlivých typů melanomů, zejména u melanomů nodulárních. Protein byl lokalizován zvláště v periferních, invazivních částech tumoru. Závěr: Sledování nesti- nu by mohlo být důležitým doplňkem ostatních melanomových markerů.
Nestin is one of intermedial filaments exprimed in proliferating progenitor cells of the CNS and PNS (central and peripheral nervous system). Postnatal reexpression of the protein occures main- ly in CNS tumors and correlates with a high grade of malignancy. The aim of our study is assess- ment of the nestin expression in benign and malignant skin melanocytic lesions with respect to presume a prognostic role of this protein. We examined 127 bioptic specimens, including 42 nodu- lar melanomas (NM), 32 superficial spreading melanomas (SSM), 10 dysplastic nevi and 43 common intradermal or dermoepidermal nevi. We proved significant increase in nestin expression in mela- noma groups, especially in nodular melanomas, where nestin was localized mainly in the periphe- ral, invasive areas of the tumor mass. Conclusion: Detection of nestin expression might be used as an additional melanocytic tumour marker.
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.
- MeSH
- exprese genu MeSH
- imunohistochemie * využití MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- nestin * metabolismus MeSH
- výzkum MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Nestin is a unique intermediate filament expressed for a short period in the developing heart. It was also documented in several cell types of the adult myocardium under pathological conditions such as myocardial infarction or fibrosis. However, circumstances of nestin re-occurrence in the diseased or aging heart have not been elucidated yet. In this work we immunohistochemically detected nestin to determine its expression and distribution pattern in the left ventricular myocardium of normotensive Wistar Kyoto (WKY) rats and in the hypertrophic ones of spontaneously hypertensive (SHR) rats, both at the age of 1 and 1.5 year. No nestin+ cells were identified in the intact myocardium of 1-year-old WKY rats, whereas in the aged 1.5-year-old WKY rats nestin+ endothelial cells in some blood vessels were discovered. In the hypertrophic myocardium of all SHR rats, nestin was rarely detected in desmin+ vimentin- cardiomyocytes and in some vimentin+ interstitial cells often accumulated in clusters, varying in intensity of desmin immunoreactivity. Moreover, nestin was infrequently expressed in the endothelial cells of some myocardial blood vessels in 1-year-old SHR rats, but not in 1.5-year-old ones. Quantitative image analysis of nestin expression in the myocardium confirmed significant increase in 1.5-year-old WKY rats and in SHR rats of both ages compared to the intact 1-year-old WKY rats. This study firstly documents nestin re-expression indicating cytoskeletal remodelling in different cell types of the aging intact and chronically pressure over-loaded hypertrophied myocardium. Our findings confirm nestin involvement in complex changes during myocardial hypertrophy and progressive aging.
- MeSH
- hypertenze metabolismus patologie MeSH
- kardiomyocyty metabolismus patologie MeSH
- krysa rodu rattus MeSH
- myokard * metabolismus patologie MeSH
- nestin * metabolismus MeSH
- potkani inbrední SHR * MeSH
- potkani inbrední WKY * MeSH
- proteiny intermediálních filament metabolismus MeSH
- proteiny nervové tkáně metabolismus MeSH
- stárnutí * metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The stem cell marker nestin (NES) is found in dividing cells of developing and regenerating tissues. Upon terminal differentiation, NES expression is diminished but may be re-expressed following injury or in cancer. Surprisingly, we recently confirmed NES as a tumour-specific marker for mature CD138(+) 38(+) plasma cells (PC) in multiple myeloma (MM). The present study analysed NES expression throughout the spectrum of MM developmental stages, starting with individuals with no haematological malignancy, through monoclonal gammopathy of undetermined significance (MGUS) and MM to plasma cell leukaemia (PCL) and MM cell lines. NES was analysed in bone marrow PC of 163 MM, four PCL and nine MGUS patients, 10 individuals with no haematological malignancy and 6 myeloma cell lines (OPM-2, RPMI-8226, MOLP-8, U-266, EJM, NCI-H929) by flow cytometry and/or real-time polymerase chain reaction or immunochemistry. We observed a tendency of increased NES expression in parallel with disease progression. NES was evaluated as a reliable marker for accurate discrimination between MM patients and the control group. High NES levels were strongly associated with the presence of 1q21 gain. For the first time, NES was demonstrated to predict worse response to conventional therapy/novel agents. These results suggest that NES might become a useful clinical parameter with an important role in MM pathogenesis.
- MeSH
- dospělí MeSH
- imunofenotypizace MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mnohočetný myelom diagnóza imunologie metabolismus patologie MeSH
- monoklonální gamapatie nejasného významu metabolismus MeSH
- nádorové biomarkery biosyntéza genetika MeSH
- nádorové buňky kultivované MeSH
- nádorové proteiny biosyntéza genetika MeSH
- nestin biosyntéza genetika MeSH
- plazmocelulární leukemie metabolismus MeSH
- prognóza MeSH
- progrese nemoci MeSH
- recidiva MeSH
- RNA nádorová genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Nestin, CD133 and ABCG2 are recently discussed as putative markers, co-expression of which might determine a cancer stem cell (CSC) phenotype in sarcomas. OBJECTIVE: Our study is focused on immunohistochemical analysis of nestin, CD133 and ABCG2 expression in rhabdomyosarcoma, Ewing sarcoma and osteosarcoma. Furthermore, we also analyzed the possible correlation of nestin, CD133 and ABCG2 expression levels with the patient outcome to identify potential prognostic values of these three putative CSC markers in the same cohorts. METHODS: Using immunohistochemistry, expression of nestin, CD133 and ABCG2 was analyzed in 24 rhabdomyosarcoma, 22 Ewing sarcoma and 10 osteosarcoma tissue samples and expression levels of these markers were correlated with clinical outcome. RESULTS: High nestin levels indicate poor prognosis in patients with Ewing sarcoma (P = 0.001), and high CD133 expression is associated with shorter survival in rhabdomyosarcoma patients (P = 0.002). In contrast, no significant relationship was found between ABCG2 expression and the clinical outcome. CONCLUSIONS: Our analysis represents the first complex study of these three putative CSCs markers together in three different types of pediatric sarcomas and showed their possible prognostic values in these tumors.
- MeSH
- ABC transportér z rodiny G, člen 2 genetika metabolismus MeSH
- antigen AC133 genetika metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu MeSH
- imunohistochemie MeSH
- Kaplanův-Meierův odhad MeSH
- kojenec MeSH
- lidé MeSH
- metastázy nádorů MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery * MeSH
- nádorové kmenové buňky metabolismus MeSH
- nestin genetika metabolismus MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- prognóza MeSH
- sarkom diagnóza genetika metabolismus mortalita MeSH
- staging nádorů MeSH
- stupeň nádoru MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Nestin, marker multipotentních prekurzorových buněk, představuje významnou dynamickou strukturu, jejíž polymerizace/depolymerizace ovlivňuje intracelulární signalizaci a podílí se na řadě klíčových buněčných procesů, jako je proliferace, migrace a přežívání buněk. Předpokládá se, že nestin hraje centrální roli v procesu karcinogeneze. Nestin je považován za možný diagnostický a prediktivní indikátor malignity solidních nádorů a potenciální marker nádorových kmenových buněk. Překvapivě byl identifikován i ve zralých CD138+38+ plazmatických buňkách (PC) mnohočetného myelomu (MM). Exprese markeru kmenových/progenitorových buněk v maligních PC, které jsou považovány za terminálně diferencované, indikuje, že nestin by mohl hrát významnou roli v patologii MM.
Nestin, a marker of multipotent precursor cells, is an important dynamic structure; its polymerization/ depolymerization influences intracellular signaling and participates in key cell processes such as proliferation, migration and cell survival. It is presumed that nestin plays a central role in carcinogenesis. It is suggested that nestin might be a suitable diagnostic and prognostic indicator of malignancy and a potential marker of cancer stem cells. Unexpectedly, nestin has been identified in mature CD138+CD38+ plasma cells (PC) of multiple myeloma patients (MM). Expression of nestin, a marker of stem/progenitor cells, in malignant PC, that are considered to be terminally differentiated, indicates that nestin might play a unique role in pathology of MM.
- Klíčová slova
- flowcytometrie, iniciující buňky, myelomové kmenové buňky,
- MeSH
- financování organizované MeSH
- lidé MeSH
- mnohočetný myelom diagnóza metabolismus patofyziologie MeSH
- nádorové biomarkery MeSH
- plazmatické buňky MeSH
- proteiny intermediálních filament analýza fyziologie MeSH
- proteiny nervové tkáně analýza fyziologie MeSH
- Check Tag
- lidé 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.
- MeSH
- CD antigeny biosyntéza genetika MeSH
- dítě MeSH
- dospělí MeSH
- financování organizované 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
- 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
BACKGROUND: Nestin is one of the intermediate filaments that are expressed in proliferating neural progenitor cells during development of the central nervous system (CNS) and peripheral nervous system. Postnatal re-expression of the protein occurs mainly under pathological conditions, including injury and neoplasia. In this study, nestin expression was detected in both benign and malignant melanocytic skin lesions and its diagnostic relevance was then evaluated. METHODS: Altogether 139 bioptic tissue samples consisting of 42 nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas, 10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi were analysed using indirect immunohistochemical staining. RESULTS: We demonstrated that nestin immunostaining was significantly increased in melanomas where it correlated with more advanced stages of the disease. CONCLUSION: We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis.
- MeSH
- financování organizované MeSH
- imunohistochemie MeSH
- lidé MeSH
- melanom krevní zásobení metabolismus MeSH
- nádorové biomarkery analýza MeSH
- nádory kůže krevní zásobení metabolismus MeSH
- patologická angiogeneze metabolismus MeSH
- pigmentový névus krevní zásobení metabolismus MeSH
- proteiny intermediálních filament biosyntéza MeSH
- proteiny nervové tkáně biosyntéza MeSH
- Check Tag
- lidé MeSH
The aim of this review is to summarize current knowledge on nestin expression in human tumors and corresponding tumor cell lines. Nestin belongs to class VI of the intermediate filaments and it is expressed primarily in mammalian nervous tissue during embryonic development. In adults, nestin occurs only in a small subset of cells and tissues. This protein has been observed in the subventricular zone of the adult mammalian brain, where neurogenesis is localized. Nestin expression has also been detected in various types of human solid tumors, as well as in the corresponding established cell lines. This article provides an up-to-date overview of tumors in which nestin has been found. Another aim of this review is to summarize recent findings on the intracellular localization of nestin in human tumor cells, especially with regard to the possible correlation between nestin expression and the malignant phenotype of transformed cells. Nestin expression in vascular endothelial cells during angiogenesis is also reviewed. Special attention is paid to the detection of nestin in cancer stem cells because this protein, together with the CD133 surface molecule, is considered to be a possible marker of cancer stem cells, especially in tumors of neuroectodermal origin.
- MeSH
- cévní endotel metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory metabolismus patologie MeSH
- patologická angiogeneze metabolismus MeSH
- proteiny intermediálních filament metabolismus MeSH
- proteiny nervové tkáně metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
