Nestin Expression In Endothelial Cells Research Articles

Role of nestin expression in angiogenesis and breast cancer progression.

Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical(IHC) analyses were carried out on 124cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki‑67. We evaluated nestin expression in tumour and endothelial cells, Ki‑67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA‑MB‑231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA‑MB‑231 and BO2 cells than in MCF-7 and SK-BR-3 cells.

Nestin-positive microvessel density is an independent prognostic factor in breast cancer.

The process of angiogenesis based on new vessel formation within the tumour area plays a significant role in the progression of breast cancer. Nestin is an intermediate filament protein and participates in the cytoskeleton organization. Nestin expression in the endothelium of blood vessels is mainly limited to newly forming vessels, thus being a more specific marker of angiogenesis than the commonly used vascular antigens. The aim of this study was to determine the prognostic value of nestin-positive microvessel density (Nes+MVD) in breast cancer patients and to confirm that nestin expression is related to newly forming tumour vessels. In this study, 137cases of ductal breast carcinoma and 19 cases of non-malignant breast tissue lesions (NBTLs) were examined. Immunohistochemical reactions were performed on paraffin sections using antibodies against nestin, CD34 and CD31 antigens. For each marker, the microvessel density (MVD) was determined. Nestin expression was also examined in human endothelial cell lines (HUVEC-SVT, HMEC-1 and HEPC-CB.1) representing a different level of endothelial cell maturity. HUVEC-SVT and HMEC-1 cells represent the endothelium of mature vessels, whereas HEPC-CB.1 cells represent the early endothelial progenitor cells (EPCs). We have demonstrated that high Nes+MVD may be associated with a more aggressive course of the disease and a poorer prognosis. We have also found a higher Nes+MVD in the cases with lymph node metastases, with higher histological grade, with advanced-stage disease and with the triple-negative(TN) breast cancer. In addition, nestin expression in vessels was associated with a shorter overall survival (OS) and earlier relapse, and in the case of OS nestin was an independent prognostic factor. Finally, we further confirmed that nestin expression in endothelial cells reflects a progenitor nature of newly forming vessels.

Hepatocellular carcinoma may display elevated nestin expression in endothelial cells: experimental study.

Nestin, a class VI intermediate filament protein, is highly expressed in the portal mesenchyme and sinusoidal endothelium of the human fetal liver, but scarcely expressed in adult portal vessel endothelium. During experimental liver regeneration, an increased number of nestin-positive parenchymal cells have been observed in the zone adjacent to the Hering canals. These parenchymal cells are regarded as hepatic stem cells or hepatoblasts, which may be involved in hepatocellular carcinogenesis. In the light of recent reports describing nestin-positive parenchymal cells in hepatocellular carcinoma, we aimed to use this tumor type as a positive control for immunohistochemical detection of nestin. Experimental study conducted at a university hospital. Hepatocellular carcinoma sections from one case were analyzed for nestin expression by immunohistochemistry using confocal microscopy. Surprisingly, a conspicuous pattern resembling liver sinusoid-like cytoarchitecture was observed upon nestin staining of endothelial cells. This pattern has not been previously described. The preliminary results shown here suggest that nestin-positive endothelial cells are located in niches of immature or proliferative cells. Moreover, nestin expression in endothelial cells of hepatocellular carcinoma enhances the role of angiogenesis in this tumor type, although the prevalence of this immunohistopathological pattern remains to be determined. Finally, hepatocellular carcinoma is an effective positive control for nestin staining in fluorescent immunohistochemistry.

Embryonic Stem Cells Markers SOX2, OCT4 and Nanog Expression and Their Correlations with Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma

Expression of embryonic stem cells (ESCs) markers (SOX2, OCT4, Nanog and Nestin) is crucial for progression of various human malignancies. The purpose of this study was to investigate the expression and prognostic impact of these molecules in nasopharyngeal carcinoma (NPC) patients by immunohistochemistry and immunofluorescence. In the present study, we found that the expression levels of SOX2, OCT4 and Nanog were highly expressed in NPC compared with the non-tumorous tissues. Furthermore, these proteins correlated significantly with several clinicalpathological factors and epithelial-mesenchymal transition (EMT)-associated indicators (E-cadherin/N-cadherin and Snail). In multivariate analyses, high expression of OCT4 (P = 0.013) and Nanog (P = 0.040), but not that of SOX2, was associated with worse survival and had strongly independent prognostic effects. Of note, OCT4 and Nanog were more frequently located at the invasive front of tumors, and correlated significantly with various aggressive behaviors including T classification, N classification, M classification and clinical stage. Furthermore, patients with co-expression of OCT4 and Nanog in the invasive front had significantly worse survival (P = 0.005). Interestingly, at the invasive front, these molecules correlated significantly with Nestin expression in endothelial cells (P<0.001). These findings provide evidence that ESCs biomarkers OCT4 and Nanog serves as independent prognostic factors for NPC. Additionally, cancer cells in the invasive front of NPC acquiring ESCs-like features should be maintained by vascular niches.

Localization of Nestin in Amygdaloid Kindled Rat: An Immunoelectron Microscopic Study

Nestin is a class VI intermediate filament protein, expressed during early embryonic development in mammals. Postnatally, nestin and its mRNA are down-regulated and gradually disappear. Recently, nestin expression has been detected in the adult nervous system, and it has been suggested that this protein may be related to neurogenesis, although, its role in the mechanism of neurogenesis is not known. The present study examined the localization of nestin in CNS tissue of the amygdaloid kindled rat by light and electron microscopy. Kindled animals showed nestin expression mainly in the piriform cortex and the perirhinal cortex. By light microscopy, nestin was shown to be expressed in astrocytes, neurons, and endothelial cells. Electron microscopy demonstrated nestin expression in endothelial cells, astrocytic perivascular end feet, the rare pericyte, neurons and oligodendrocytes. We conclude that epilepsy causes widespread nestin expression in many cell types in the CNS, including non-neural cells.