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

NG2 is a membrane-associated chondroitin sulfate proteoglycan with a core protein of 300 kD. Previously it was shown immunochemically that the core protein of NG2 can bind type VI collagen (Stallcup, W., Dahlin, K., and P. Healy. 1990. J. Cell Biol. 111:3177-3188). We have extended our studies on the interaction of NG2 and type VI collagen by transfecting cells with the full-length rat NG2 cDNA. B28 rat neural cells and U251MG human glioma cells used for transfection do not synthesize NG2. Both cell lines secrete type VI collagen into tissue culture medium but do not anchor it at the cell surface. Upon transfection of these cells with the NG2 cDNA, NG2 was correctly localized to the cell surface. Furthermore, type VI collagen could now be detected on the surface of NG2-positive cells in a pattern that coincided with that of NG2. This ability of NG2 to anchor type VI collagen to the cell surface could be abolished by incubating the cells in the presence of anti-NG2 monoclonal antibodies. These findings indicate that NG2 functions as a cell surface receptor for type VI collagen and may play a role in modulating the assembly of pericellular matrix.
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PMID:Expression of NG2 proteoglycan causes retention of type VI collagen on the cell surface. 830 32

Previous studies have established that the NG2 proteoglycan binds directly to type VI collagen. To further our understanding of the biochemical and functional significance of this interaction we have used NG2 cDNA to construct a series of NG2 mutants with deletions spaced throughout the entire length of the 260-kDa NG2 core protein. Following transfection of these mutant cDNAs into B28 glioma cells, we determined the ability of mutant NG2 molecules to anchor type VI collagen on the cell surface. Eight of 11 transfectant populations were able to anchor type VI collagen. The three NG2 variants incapable of anchoring type VI collagen have deletions clustered within the central one-third of the NG2 ectodomain. These deletions identify a 469-amino-acid domain of NG2 responsible for binding of type VI collagen. Functional consequences of the NG2-type VI collagen interaction were explored by testing the relative ability of NG2-transfected and untransfected glioma cells to migrate toward type VI collagen. NG2-expressing cells exhibited a greater migratory response toward type VI collagen than their NG2-negative counterparts. This enhanced migration could be specifically inhibited with NG2 antibodies. Furthermore, glioma cells expressing NG2 in which the collagen-binding domain was deleted failed to exhibit this enhanced migration, whereas NG2 mutants in which non-collagen-binding regions were deleted continued to exhibit increased chemotaxis toward the type VI collagen. These comparisons confirm the importance of the central collagen-binding domain in mediating functionally important interactions between NG2 and type VI collagen.
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PMID:A central segment of the NG2 proteoglycan is critical for the ability of glioma cells to bind and migrate toward type VI collagen. 928 75

The early events in neoplastic transformation can be understood only by comparison of the neoplastic cell with its nontransformed counterpart. The most common central nervous system gliomas traditionally are thought to arise from mature astrocytes and oligodendrocytes. We examined the possibility that gliomas arise from a population of glia that has properties of oligodendrocyte progenitors. These glial cells express the NG2 chondroitin sulfate proteoglycan and the alpha receptor of platelet-derived growth factor in vivo. We identified NG2 and the alpha receptor of platelet-derived growth factor expression in tissue from seven of seven oligodendrogliomas, three of three pilocytic astrocytomas, and one of five glioblastoma multiforme. These data provide evidence that glial tumors arise from glial progenitor cells. Molecules expressed by these progenitor cells should be considered as targets for novel therapeutics.
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PMID:Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors. 1046 13

The expression and function of NG2, a transmembrane chondroitin sulfate proteoglycan was studied in human gliomas of various histological types in culture using immunocytochemistry and flow cytometry. NG2 was differentially expressed in the neoplasms, with higher expression in high compared to low-grade gliomas. In acutely isolated cells from human biopsies, NG2 +ve and NG2 -ve populations were morphologically distinct from each other, and NG2 +ve cells were more proliferative than NG2 -ve cells. The mitogens platelet derived growth factor (PDGF-AA) and basic fibroblast growth factor (bFGF) added in combination to serum-free medium (SFM) upregulated NG2 expression on glioblastoma multiforme cells in culture but had little effect on NG2 expression on the anaplastic astrocytoma cells. Furthermore, NG2 was colocalised with the platelet derived growth factor alpha receptor (PDGFalphaR) and antibody blockade of the PDGF-alphaR ablated NG2 expression on the glioblastoma multiforme cells, suggesting that increased NG2 expression in the presence of PDGF-AA is mediated via the PDGF-alphaR. Assays of migration and invasion indicate that NG2 +ve glioma cells migrated more efficiently on collagen IV and that NG2 -ve cells were more invasive than their NG2 +ve counterparts. The results indicate that NG2 may be, respectively, positively and negatively related to the proliferative and invasive capacity of glioma cells. Thus, expression of the NG2 proteoglycan may have major implications for malignant progression in glial neoplasms and may prove a useful target for future therapeutic regimens.
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PMID:The NG2 chondroitin sulfate proteoglycan: role in malignant progression of human brain tumours. 1057 5

Diffusely infiltrating astrocytic tumours of the central nervous system (CNS) are the most frequent intracranial neoplasms and account for more than 60% of all primary brain tumours in man. Until recently, it was generally accepted that the glial component of the mature CNS, consisted of differentiated astrocytes, ependymal cells, oligodendrocytes and the non-neuro-ectodermal microglial cells. There exists a recently recognised population of glial cells that express the NG2 proteoglycan (NG2 cells). NG2 cells are dynamic and undergo rapid morphological changes in response to a variety of CNS pathologies. They are highly motile cells, which interact with various extracellular matrix (ECM) in association with the integrin receptors. During angiogenesis and response to tissue injury, NG2 precursor cells are recruited to sites where vessel growth and repair are occurring. NG2 is over-expressed by both tumour cells and pericytes on the blood vessels of malignant brain tumours. The function of NG2 cells in the CNS, and the notion of them as a source of and/or lineage marker for some gliomas are discussed. In addition, their possible role in glioma angiogenesis, proliferation and invasion will be considered as will their value in provision of targets for clinical and pre-clinical therapeutic strategies in brain tumours.
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PMID:NG2 precursor cells in neoplasia: functional, histogenesis and therapeutic implications for malignant brain tumours. 1450 Dec 20

Tumour angiogenesis is a tightly regulated process involving cross-talk between tumour cells and the host tissue. The underlying mechanisms that regulate such interactions remain largely unknown. NG2 is a transmembrane proteoglycan whose presence on transformed cells has been demonstrated to increase proliferation in vitro and angiogenesis in vivo. To study the effects of NG2 during tumour growth and progression, we engineered an NG2 positive human glioma cell line (U251-NG2) from parental NG2 negative cells (U251-WT) and implanted both cell types stereotactically into immunodeficient nude rat brains. The tumours were longitudinally monitored in vivo using multispectral MRI employing two differently sized contrast agents (Gd-DTPA-BMA and Gadomer) to assess vascular leakiness, vasogenic oedema, tumour volumes and necrosis. Comparisons of Gd-DTPA-BMA and Gadomer revealed differences in their spatial distribution in the U251-NG2 and U251-WT tumours. The U251-NG2 tumours exhibited a higher leakiness of the larger molecular weight Gadomer and displayed a stronger vasogenic oedema (69.9 +/- 15.2, P = 0.018, compared to the controls (10.7 +/- 7.7). Moreover, immunohistochemistry and electron microscopy revealed that the U251-NG2 tumours had a higher microvascular density (11.81 +/- 0.54; P = 0.0010) compared to controls (5.76 +/- 0.87), with vessels that displayed larger gaps between the endothelial cells. Thus, tumour cells can regulate both the function and structure of the host-derived tumour vasculature through NG2 expression, suggesting a role for NG2 in the cross-talk between tumour-host compartments.
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PMID:NG2 expression regulates vascular morphology and function in human brain tumours. 1625 23

Previous work has demonstrated the ability of the NG2 proteoglycan, a component of microvascular pericytes, to stimulate endothelial cell motility and morphogenesis. This function of NG2 depends on formation of a complex with galectin-3 and alpha3beta1 integrin to stimulate integrin-mediated transmembrane signaling. In addition, the co-expression of galectin-3 and NG2 in A375 melanoma cells suggests that the malignant properties of these cells may be affected by interaction between the two molecules. Here, we extend the theme of co-expression and interaction of NG2 and galectin-3 to human glioma cells. We also establish a molecular basis for the NG2/galectin-3 interaction. The C-terminal carbohydrate recognition domain of galectin-3 is responsible for binding to the NG2 core protein. Within the NG2 extracellular domain, the membrane-proximal D3 segment of the proteoglycan contains the primary binding site for interaction with galectin-3. The interaction between galectin-3 and NG2 is a carbohydrate-dependent one mediated by N-linked rather than O-linked oligosaccharides within the D3 domain of the NG2 core protein. These studies establish a foundation for attempts to reduce the aggressive properties of tumor cells by disrupting the NG2/galectin-3 interaction.
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PMID:Molecular basis of interaction between NG2 proteoglycan and galectin-3. 1636 73

Chemotherapy in itself is suspected to cause the development or selection of drug-resistant tumor cells, which have more aggressive phenotypes. The authors investigated the differential changes of gene expression in the 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant subline of the C6 rat glioma (C6AR2), which was established from C6 rat glioma cells by exposure to ACNU in vitro. The resistance to ACNU of C6AR2 was confirmed by MTS assay. The increased expression of O6-methylguanine-DNA methyltransferase in C6AR2 cells was shown using RT-PCR. C6AR2 cells displayed a higher proliferative activity relative to C6 cells. Analysis with cDNA array showed that 19 genes were transcriptionally up-regulated and 16 genes down-regulated in C6AR2 cells compared to C6 cells. They belonged to various functional classes of genes beside the drug-resistant system. Among them, the down-regulation of several genes in C6AR2 cells, including c-kit, pleiotrophin, platelet-derived growth factor receptor-alpha, peripheral myelin protein-22 and NG2 chondroitin sulfate proteoglycan, which are expressed originally in developmental glial lineages, were verified using semi-quantitative RT-PCR. In addition, the gene expression of astroglial intermediate filament proteins, including GFAP, vimentin and nestin, were decreased in C6AR2 cells relative to C6 cells in semi-quantitative RT-PCR and immunocytochemistry. These findings may represent an undifferentiated state of ACNU-resistant glioma cells and a more aggressive phenotype in recurrent tumors following chemotherapy.
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PMID:Gene expression profiles of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant C6 rat glioma cells. 1664 21

We characterized the expression and functional properties of the ADP-sensitive P2Y(1) and P2Y(12) nucleotide receptors in glioma C6 cells cultured in medium devoid of serum for up to 96 h. During this long-term serum starvation, cell morphology changed from fibroblast-like flat to round, the adhesion pattern changed, cell-cycle arrest was induced, extracellular signal-regulated kinase (ERK1/2) phosphorylation was reduced, Akt phosphorylation was enhanced, and expression of the P2Y(12) receptor relative to P2Y(1) was increased. These processes did not reflect differentiation into astrocytes or oligodendrocytes, as expression of glial fibrillary acidic protein and NG2 proteoglycan (standard markers of glial cell differentiation) was not increased during the serum deprivation. Transfer of the cells into fresh medium containing 10% fetal bovine serum reversed the changes. This demonstrates that serum starvation caused only temporary growth arrest of the glioma C6 cells, which were ready for rapid division as soon as the environment became more favorable. In cells starved for 72 and 96 h, expression of the P2Y(1) receptor was low, and the P2Y(12) receptor was the major player, responsible for ADP-evoked signal transduction. The P2Y(12) receptor activated ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulated Akt activity. These effects were reduced by AR-C69931MX, a specific antagonist of the P2Y(12) receptor. On the other hand, Akt phosphorylation increased in parallel with the low expression of the P2Y(1) receptor, indicating the inhibitory role of P2Y(1) in Akt pathway signaling. The shift in nucleotide receptor expression from P2Y(1) to P2Y(12) would appear to be a new and important self-regulating mechanism that promotes cell growth rather than differentiation and is a defense mechanism against effects of serum deprivation.
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PMID:Expression and functional characterization of P2Y1 and P2Y12 nucleotide receptors in long-term serum-deprived glioma C6 cells. 1735 84

Many human gliomas carry markers characteristic of oligodendrocyte progenitor cells (such as Olig-2, PDGF alpha receptor and NG2 proteoglycan), suggesting these progenitors as the cells of origin for glioma initiation. This review considers the potential roles of the NG2 proteoglycan in glioma progression. NG2 is expressed not only by glioma cells and by oligodendrocyte progenitors, but also by pericytes associated with the tumor microvasculature. The proteoglycan may therefore promote tumor vascularization and recruitment of normal progenitors to the tumor mass, in addition to mediating expansion of the transformed cell population. Along with potentiating growth factor signaling and serving as a cell surface receptor for extracellular matrix components, NG2 also has the ability to mediate activation of beta-1 integrins. These molecular interactions allow the proteoglycan to contribute to critical processes such as cell proliferation, cell motility and cell survival.
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PMID:A role for the NG2 proteoglycan in glioma progression. 1926 11


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