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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor cells of a particular tissue may show a pattern of gene expression characteristic of the precursor cells of this tissue. To test this proposition for tumors of the central nervous system (CNS) we have used immunohistochemistry to analyze the expression of nestin in primary human CNS tumors and corresponding nonneoplastic brain tissue. Nestin defines a recently discovered sixth class of intermediate filament proteins and in the rat is expressed predominantly in CNS stem cells. In the adult nonneoplastic human brain we have detected only nestin expression in occasional endothelial cells. In contrast, a variety of primary CNS tumors contained substantially elevated nestin levels. The nestin-positive cells in the tumor tissue were tumor cells and/or endothelial cells. Glioblastomas expressed higher nestin levels than less malignant gliomas. This may indicate a correlation between nestin expression and malignancy within the glioma tumor group. In the primitive neuroectodermal class of tumors we observed both nestin-expressing and nonexpressing tumors, suggesting that nestin expression could be used to further characterize this complex and heterogeneous tumor group. Nine metastatic carcinomas were studied, and none showed nestin immunoreactivity in tumor cells. In conclusion, our data support the notion that primary CNS tumors share gene expression patterns with primitive, undifferentiated CNS cells and that nestin, like other intermediate filaments, may be useful in tumor diagnosis.
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PMID:Expression of the class VI intermediate filament nestin in human central nervous system tumors. 138 41

Nestin is a recently described member of the intermediate filament (IF) protein family that is especially abundant in neuroepithelial stem cells of the rat. The studies described here examine this class VI IF protein in the normal human developing central nervous system (CNS), human brain tumor-derived cell lines, and tissue samples of human CNS tumors. Human nestin exhibited biochemical and immunochemical properties similar to those of rat nestin. Further, as in the rat, nestin was detected immunohistochemically in several different types of immature human CNS cells, i.e. germinal matrix cells, neuroepithelial cells lining the central canal, radial glia and vascular cells. Nestin appeared in these cells at the earliest gestational age (i.e., 6 weeks) examined here and then it declined in all but the vascular cells at later embryonic stages. Nestin also was detected by immunocytochemistry in 6 of 7 primitive neuroectodermal tumor cell lines and in both of 2 malignant glioma cell lines examined. In these cell lines, nestin co-localized incompletely with bundles of IFs containing other IF proteins (i.e., vimentin, glial filament, neurofilament). Nestin was ubiquitous in a wide variety of brain tumors, but was most prominent in gliomas. The transient expression of nestin in primitive neuroepithelial cells at early stages of human embryogenesis and its abundance in neuroepithelial tumors suggest a role for nestin IFs in cellular events that precede the exit of embryonic CNS stem cells from the cell cycle and the commitment of the progeny of these stem cells to a specific lineage. The subsequent induction of different members of the IF protein family in phenotypically distinct CNS cells (i.e. neurons, glia) and the elimination of nestin from almost all differentiated CNS cells, imply that different classes of IFs subserve functions that are closely linked to the maturational state, as well as the lineage, of CNS cells.
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PMID:Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells. 153 85

For glioma- and glioblastoma-specific gene expression, we utilized a nestin regulatory element whose activity was evaluated by the reporter gene lacZ. Nestin is a 38-kDa intermediate filament protein, and is expressed specifically in the neuroepithelial stem cells. Nestin is detected in gliomas and glioblastomas, but not in normal brain tissue. We constructed a nestin gene regulator by placing nestin's second intron before the 5' upstream region (2iNP). To obtain enhanced expression of this tissue-specific regulator, we utilized the adenovirus double-infection method with a Cre-loxP on/off switching system. We constructed a 'regulator' vector, Ax2iNPNCre, which expresses Cre recombinase under the control of the nestin regulatory element, 2iNP. A 'reporter' vector, AxCALNLNZK, expresses lacZ under the control of a strong CAG promoter when the stuffer sequence has been removed by Cre recombinase at a pair of loxP sites. We used seven human glioma/glioblastoma cell lines: U251, KG-1C, NGM5, U87 MG, LN-Z308, NP-2 and T98G. Of these, nestin was expressed highly in U251 and KG-1C, less in NGM5, and undetectably in the other four lines. With the use of the two adenovirus vectors, we found X-gal staining and high nestin regulator-promoted beta-galactosidase activities in four of the seven glioma/glioblastoma cell lines. Staining was strong in U251, KG-1C and NGM5, and less in U87 MG. LacZ expression was nearly undetectable in the non-glioma cell line, HeLa, but a little in COS-7. The adenovirus double-infection method, which uses a nestin regulator, is applicable for glioma/glioblastoma-specific expression.
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PMID:Glioma/glioblastoma-specific adenoviral gene expression using the nestin gene regulator. 1080 92

Nestin is one of the intermediate filaments abundantly produced in the developing central nervous system and somites in the embryonic stage. Nestin is also reportedly detected in gliomas/glioblastomas. We retested nestin expression in brain tumors having a range of malignancy grades using immunostaining. The intensity of nestin immunostaining roughly paralleled the malignancy grade of the gliomas. However, many tumors were negative for nestin immunostaining, while nestin immunostaining was invariably detected in tumor endothelium regardless of glioma malignancy grades or brain tumor types. We suspected that angiogenic epithelial cells may express nestin, and we found that nestin was highly positive in bovine aortic endothelial cells in static culture. However, nestin expression decreased when the endothelial cells underwent laminar shear stress flow, under which endothelial cells exhibit differentiated features and a decreased rate of growth. Because nestin is highly expressed in growing endothelial cells, we examined its expression in hemangioblastomas because hemangioblasts are thought to be a precursor for angiogenic epithelial cells. As expected, nestin immunostained strongly in all four samples of hemangioblastomas. We suggest that nestin is not only a marker for neuroepithelial stem cells and glioma cells but also for tumor endothelial cells during rapid growth.
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PMID:Nestin as a marker for proliferative endothelium in gliomas. 1189 13

To investigate adult neural stem cell (NSC) biology in relation to glioma, the C6 glioma cell line was tagged with green fluorescent protein (GFP) and inoculated into the brain of adult rats. The in vivo biological response of the brain to glioma was studied using immunohistochemical analysis of the subventricular zone (SVZ), peritumoral areas, and glioma. Nestin immunoreactive cells were found infiltrating glioma, but the distribution of abnormal immunoreactivity was restricted to the dorsal and medial border of the tumor relative to the ipsilateral ventricle. The SVZ was found to be hypertrophic, hypercellular, and up-regulated nestin expression. Furthermore, a dense contiguous population of nestin immunoreactive cells could be found streaming from ipsilateral dorsal tip of the SVZ, tracking along the ventral margin of the corpus callosum, and fanning out to encompass and infiltrate the proximal tumor border. Although most cells were either nestin or glial fibrillary acidic protein (GFAP) immunoreactive in the SVZ and along the ventral margin of the corpus callosum, the number of cells co-expressing both markers increased proportionally as the tumor was approached so that the predominant cell population along the proximal tumor border was GFAP immunoreactive. Finally, we demonstrated that a significant proportion of cells found in areas of abnormal immunoreactivity were proliferating, especially in peritumoral areas. In summary, there is an induction of neuropoietic activity in a rat intracranial glioma model that results in an infiltration and accumulation of abnormal nestin and GFAP expressing cells with proliferative potential along the dorsal and medial border of intracranial C6 glioma.
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PMID:Up-regulation of neuropoiesis generating glial progenitors that infiltrate rat intracranial glioma. 1573 12

Angiogenesis is a key event in the natural progression of gliomas. Nestin, a marker for multipotential neuroepithelial stem cells, is detected in neuroepithelial tumors and in proliferating endothelial cells (ECs) and is involved in the early stages of lineage commitment, proliferation and differentiation. Nestin expression is correlated with proangiogenic chemokines (CXCL12 and its receptor CXCR4) and growth factors (VEGF, PDGF-B and its receptor PDGFRbeta). VEGF expression upregulates CXCR4 on endothelial cells, binding the chemokine SDF1/CXCL12 (Stromal Derived Factor) that has a role on angiogenesis and chemotaxis of endothelial cells; PDGF (platelet-derived growth factor) and PDGFRbeta are also crucial by increasing the expression of VEGF. We performed a retrospective study on the presence and role of nestin-expressing cells in 102 patients with glioma, relating the findings to VEGF, CXCL12, PDGFRbeta expression and to clinical outcome (time to tumor progression-TTP and survival time-ST). Our results suggest that in gliomas the detection of proliferating ECs expressing nestin correlates to histological malignancy grade and clinical outcome. Also, the expression of CXCL12 in low-grade gliomas was the only factor associated with a significantly shorter TTP, suggesting a role of this chemokine in angiogenic shift and/or disease progression.
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PMID:Nestin, PDGFRbeta, CXCL12 and VEGF in glioma patients: different profiles of (pro-angiogenic) molecule expression are related with tumor grade and may provide prognostic information. 1761 2

Wnt5a operates as either a tumor suppressor or a tumor stimulator, according to tumor type. The functions of Wnt5a in human glioblastoma (GBM) have yet to be determined. We initially evaluated the expression of Wnt5a in human glioma. The results of immunohistochemical analyses have revealed that Wnt5a expression was higher in human GBM than in normal brain tissue and low-grade astrocytoma. In order to assess the role of Wnt5a on proliferation in human glioblastoma cells, we employed U87MG and GBM-05, a newly established GBM cell line. GBM-05 was established from a patient diagnosed with GBM. GBM-05 cells were shown to express Nestin, but did not express GFAP and Map2ab. GBM-05 cells formed infiltrating brain tumors after being intracerebrally transplanted into nude mice, and xenotransplanted GBM-05 cells were observed to differentiate into neuronal and astrocyte lineages. Wnt5a expression in the xenotransplanted tumors was higher than that detected in the surrounding brain tissues. The overexpression of Wnt5a increased the proliferation of GBM-05 and U87MG in vitro. By way of contrast, the downregulation of Wnt5a expression as the result of RNA interference reduced proliferation from GBM-05 and U87MG cells in vitro, and reduced tumorigenicity in vivo. Our data indicate that Wnt5a signaling is an important regulator in the proliferation of human glioma cells.
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PMID:Role of Wnt5a in the proliferation of human glioblastoma cells. 1770 79

Glioblastoma stem cells are able to reform original glioblastoma and express the neural stem cell marker CD133 and Nestin. They can self-renew and proliferate in tumor sphere medium containing EGF, bFGF and LIF that is known to be permissive for stem cell proliferation. In this study, we found that neurosphere-like colonies appeared after the human primary glioblastoma cells had been switched into pure DMEM/F12 medium. We investigated whether tumor spheres formed in pure DMEM/F12 medium possess the characteristics of glioblastoma stem cells. We identified that the tumor sphere cells were cancer stem cells of glioblastoma and they can self-renew and proliferate in pure DMEM/F12 medium. Glioblastoma cells can secrete several factors that result in autocrine motility signaling and stimulate glioma invasion. We hypothesized that an essential autocrine signal promotes the self-renewal and proliferation of human glioblastoma stem cells in pure DMEM/F12 medium. Then, expression of EGF and bFGF in glioblastoma stem cells were analyzed. Both the mRNA and protein of EGF and bFGF were detected in three human glioblastoma stem cells. Our findings suggest that autocrine of EGF and bFGF may sustain the self-renewal of glioblastoma stem cells.
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PMID:Autocrine factors sustain glioblastoma stem cell self-renewal. 1914 17

Accumulating evidence suggests that in several types of brain tumors, including glioma, only a phenotypic subset of tumor cells called brain cancer stem cells (BCSCs) may be capable of initiating tumor growth. Recently, the isolation of side population (SP) cells using Hoechst dye has become a useful method for obtaining cancer stem cells in various tumors. In this study, we isolated cancer stem-like cells from human glioma cell lines using the SP technique. Flow cytometry analysis revealed that SK-MG-1, a human glioblastoma cell line, contained the largest number of SP cells among the five glioma cell lines that were analyzed. The SP cells had a self-renewal ability and were capable of forming spheres in a neurosphere culture medium containing EGF and FGF2. Spheres derived from the SP cells differentiated into three different lineage cells: neurons, astrocytes and oligodendrocytes. RT-PCR analysis revealed that the SP cells expressed a neural stem cell marker, Nestin. The SP cells generated tumors in the brains of NOD/SCID mice at 8weeks after implantation, whereas the non-SP cells did not generate any tumors in the brain. These results indicate that SP cells isolated from SK-MG-1 possess the properties of cancer stem cells, including their self-renewal ability, multi-lineage differentiation, and tumorigenicity. Therefore, the SP cells from SK-MG-1 may be useful for analyzing BCSCs because of the ease with which they can be handled and their yield.
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PMID:Isolation of cancer stem-like cells from a side population of a human glioblastoma cell line, SK-MG-1. 1991 93

Cancer stem-like cells (CSLCs) are potential targets for treatment of glioblastoma multiforme (GBM) due to their role in tumorigenesis and recurrence. In this study, we investigated the inhibitory effect of arsenic trioxide (As(2)O(3)) on CSLCs of GBM in human glioma cell lines (U87MG, U251MG and U373MG) in vivo and in vitro. Immunofluorescence staining and flow cytometry revealed that the percentage of Nestin-positive cells in the aforementioned cell lines was diminished by 12%, 14% and 7%, respectively, after treatment with 2 microM As(2)O(3). Furthermore, we used soft-agar in U87MG and tumor xenografts in nude mice to demonstrate the ability of As(2)O(3) to inhibit the formation of tumor in the three cell lines. These results indicate the negative regulation of CSLCs by As(2)O(3). In addition, a Western blot analysis revealed decreased levels of Notch1 and Hes1 proteins due to As(2)O(3) treatment. We conclude that As(2)O(3) has a remarkable inhibitory effect on CSLCs in glioma cell lines in vivo and in vitro; in addition, we determined that the mechanism of CSLC inhibition involves the deregulation of Notch activation.
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PMID:Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas. 1996 20


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