Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas.
ABSTRACT Nestin, a class VI intermediate filament protein, was originally described as a neuronal stem cell marker during central nervous system development. Nestin is expressed in gliomas, and its expression levels are higher in gliomas with high WHO histopathological classification grades than in those with low grades. In the present study, we examined whether nestin regulates the biological activities of human glioma cells. Immunohistochemically, the nestin expression patterns in 10 human glioblastoma patients were examined. The expression levels of nestin in A172, a human high-grade glioma cell line, and KG-1-C, a human low-grade glioma cell line, were examined using real-time PCR, Western blot and immunofluorescence analyses. An expression vector carrying a short hairpin RNA targeting nestin was stably transfected into A172 (Sh) cells. The effects of decreased expression levels of nestin in Sh cells on cell growth, migration, invasion, adhesion to extracellular matrices and fibrillar actin expression on three-dimensional culture plates were examined. The nestin expression vector was transiently transfected into KG-1-C (Nes) cells, and the effects of the nestin overexpression on cell growth and migration were examined. Nestin was expressed in the cytoplasm of the glioblastoma cells in all cases examined. Sh cells showed marked decreases in the expression levels of nestin mRNA and protein, and the growth rate of Sh cells was lower than that of sham (Sc) cells. In contrast, the adhesion activity of Sh cells to types I and IV collagens, fibronectin and laminin was higher than that of Sc cells. Fibrillar actin was clearly detected at the periphery of colonies of Sh cells at the attachment sites on three-dimensional culture plates. The migration and invasion of Sh cells were markedly inhibited compared with those of Sc cells. In contrast, the levels of nestin expression markedly increased in the Nes cells, which were transiently transfected with the nestin expression vector. The growth rate and motility of Nes cells were higher than those of the mock cells. In conclusion, nestin plays important roles in cell growth, migration, invasion and adhesion to extra-cellular matrices in glioma cells. Nestin may serve as a novel candidate for molecular-targeted therapy for gliomas, including glioblastomas.
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ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high incidence of distant metastasis. Recent studies have shown that cancer stem cells (CSCs), which have the potential to self-renew and are pluripotent, are crucially important in cancer cell growth, invasion, metastasis, and recurrence. Recently, several CSC-specific markers for pancreatic cancer have been reported, including CD133, CD24, CD44, CXCR4, EpCAM, ABCG2, c-Met, ALDH-1, and nestin, but their use is controversial. Nestin is one of the class VI intermediate filament proteins and a marker of exocrine progenitors of normal pancreatic tissue. Activated mutations of K-ras in nestin-positive progenitors of pancreatic tissue have been reported to induce cell growth in vitro and induce the formation of precancerous pancreatic lesions. We have reported that downregulation of nestin in PDAC cells inhibits liver metastasis in vivo. Nestin may modulate the invasion and metastasis of nestin-positive progenitor cells during PDAC development and may serve as a novel target for suppressing invasion and metastasis in PDAC. In this review, we summarize what is known about the correlation between PDAC and CSC markers, including nestin.Medical Molecular Morphology 06/2012; 45(2):59-65. · 1.17 Impact Factor
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ABSTRACT: Nestin expression reportedly correlates with aggressive growth, metastasis, poor prognosis and presence of cancer stem cells (CSCs) in various tumors. In this study, we determined the expression and role of nestin in cervical intraepithelial neoplasia (CIN) and cervical cancer. We performed immunohistochemical and in situ hybridization analyses of nestin in 26 cases for each stage of CIN and 55 cervical cancer tissue samples. To examine the role of nestin in cervical cancer cells, we stably transfected expression vectors containing nestin cDNA into ME-180 cells. We studied the effects of increased nestin expression on cell proliferation, cell motility, invasion as well as sphere and soft agar formation. Nestin was not localized in the squamous epithelium in normal cervical tissues, but it was weakly expressed in the basal squamous epithelium of CIN 1. In CIN 2, nestin was localized to the basal to lower 2/3 of the squamous epithelium, whereas in CIN 3, it was localized to the majority of the squamous epithelium. Nestin was detected in all cases of invasive cervical cancer. Nestin mRNA was expressed in both ME-180 and CaSki cells. Growth rate, cell motility and invasion ability of stably nestin-transfected ME-180 cells were not different from empty vector-transfected ME-180 (mock cells). However, the nestin-transfected ME-180 cells formed more colonies and spheres compared to the mock cells. These findings suggest that nestin plays important roles in carcinogenesis and tumor formation of cervical cancer cells. Nestin may closely correlate with regulation of CSCs.International Journal of Oncology 05/2012; 41(2):441-8. · 2.66 Impact Factor
- Medical Molecular Morphology 02/2013; · 1.17 Impact Factor