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

During neurulation, neural crest cells migrate to many regions of the body to give rise to a wide variety of cell types. Many premigratory neural crest cells are pluripotent, their potency for differentiation being gradually restricted as they migrate along definite pathways and interact with factors present in the microenvironment. Effects of growth factors on these cells have been discussed in the present review. Mediation of growth factors in differentiation varies with the cell type. Growth factors exert a direct influence on the differentiation of neural and other related neural crest-derived tissues such as endocrinal tissues but evidence for such influences on neural crest-derived mesenchymal tissues is limited. For example, NGF, BDNF, and other factors present in neural tube extracts and glioma cell conditioned medium are essential for the differentiation of sensory neurons. Similarly, NGF, insulin, IGFs and possibly other undescribed factors are necessary for the differentiation of sympathetic neurons. IGFs also enhance the proliferation of mesenchymal derivatives of both neural crest and mesodermal origin. Glucocorticoid-mediated differentiation of neural crest-derived chromaffin endocrine cells that are ontogenetically closely related to sympathetic neurons can be inhibited by NGF, and chromaffin cells can be induced to express the neuronal phenotype by NGF. Some growth factors, such as NGF, act on neural crest- and not on placodally-derived neurons, whether the former are sensory or sympathetic. Placodal sensory neurons possess NGF receptors, but only display a limited response to NGF, perhaps because of low affinity of the receptors. Other growth factors, such as BDNF, selectively act upon sensory neurons, whether neural crest- or placodally-derived. Although extracellular matrix products play a role in initiating the differentiative process, signals from growth factors are necessary for the establishment of the functionally competent phenotype of neural crest-derived neurons, a situation that does not apply for neural crest-derived mesenchymal cells. It is interactions with ECM components deposited by epithelia that govern the differentiation of mesenchymal derivatives. Growth factors do effect proliferation of mesenchymal derivatives and inhibit mesenchymal differentiation. Although direct involvement of single growth factors in transformation o f one mesenchymal phenotype to another has not been reported so far, their localization at sites of epithelial-mesenchymal interactions in palate teeth and mandible, and the ability of excess growth factors to interrupt normal development is suggestive of their possible involvement. One group of growth factors, BMPs, can influence differentiation of cartilage, including those of neural crest origin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of growth factors on the differentiation of neural crest cells and neural crest cell-derivatives. 180 64

Gliomas are known to express over a hundred antigens, and no doubt make many more unknown antigens. Major categories of glioma cell antigens include glial antigens, ECM antigens, muscle antigens, melanoma antigens, "tumor-specific" antigens, and cellular proliferation antigens. A strikingly low number of cultured gliomas express glial antigens. They commonly express not only ectodermal, but also mesenchymal ECM antigens. Tumor-specific antigens have been an elusive goal of neuro-oncologists, but there are bright new prospects in need of further study. These include direct screening of hybridoma supernatants on glioma tissue and targeting glycolipids, glycoproteins, and oncogene products. Cellular proliferation antigens will become increasingly important in predicting prognosis of gliomas. Proliferation antigens of cultured gliomas are under intense scrutiny at present. The extent and evolution of antigenic heterogeneity of neoplastic cells in gliomas raise basic biologic questions with profound clinical ramifications. Individual glioma cell lines may generate more than 30 subtypes of cells with minor to major differences in antigen expression. These include expression of antigens representing multiple different cell lineages. Mesenchymal drift is the tendency of gliomas to progressively lose glial and gain mesenchymal features. Models of in vivo mesenchymal drift occur in glioma cell culture where mechanisms are more easily investigated than in situ. Neither exogenous protein absorption nor fibroblast overgrowth explain the phenomenon. Cells with the mesenchymal marker, fibronectin, overgrow GFAP-positive cells during explanation of gliomas. Many of these fibronectin-positive cells express cytologic and growth characteristics of neoplasia. The source of these cells is unknown. A leading candidate for the source of these neoplastic fibronectin-positive cells is the proliferation of vascular and mesenchymal cell elements of glioma tissue commonly called "endothelial proliferations". However, these elements in tissue do not display the same abnormalities of neoplasia as the fibronectin-positive cells in culture. Understanding this "tissue/explant paradox" may solve the conundrum of mesenchymal drift. In the absence of a counterpart in tissue of these neoplastic fibronectin-positive cells so abundant in glioma cell cultures, mechanisms of mesenchymal drift other than overgrowth of neoplastic mesenchyme must be considered. The occurrence of "dual cells" which express antigenic markers of entirely different cellular lineages suggests the possibility that neoplastic glia generate mesenchymal drift by altered gene expression. Various studies which suggest the capacity of cultured gliomas to alter phenotypic expression of their genes are critically examined and their relevance to mesenchymal drift discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Patterns of antigenic expression of human glioma cells. 193 88

The effect of non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (commonly known as aspirin), salicylic acid, piroxicam and indomethacin on the growth of rat glioma cells (RG 2) in vitro and aspirin in vivo was studied. The in vitro studies reveal that aspirin and salicylic acid strongly inhibit growth of rat glioma (RG 2) cells in concentrations used in medicine for treatment of rheumatic diseases. On the other hand, indomethacin and piroxicam had no effect, indicating that the inhibitory effect on tumor growth is not due to the inhibition of prostaglandin synthesis. The synthesis of ATP was markedly reduced (34% of control) in the presence of drugs, whereas protein synthesis measured as 3H-leucine incorporation was slightly more inhibited (73% of control) than cell growth. Aspirin administered to Fischer 344 rats inhibited growth of RG 2 cells inoculated into the caudate nucleus in vivo, both when administered the day before inoculation of tumor cells and when tumors had formed, i.e. 5 days post inoculation.
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PMID:Growth inhibition of rat glioma cells in vitro and in vivo by aspirin. 756 4

An induction of laminin in the confrontation zone between tumor cells and normal brain tissue has been observed in our model systems in vivo and in vitro. In order to study the effects of ECM components on glioma-cell migration and invasion, we have used 2 lacZ-transfected glioma cell lines, AN1/lacZ and U-251 /lacZ. Cell migration from multicellular spheroids was studied using different types of media: DMEM with 10% serum, Ultra Culture medium, and filtrated DMEM with serum in which the protein fraction > 100 kDa had been removed by ultrafiltration. Laminin, fibronectin and collagen type-IV were individually added to the different media, and cell migration from the spheroids was studied. The results show that cell migration in both cell lines, was stimulated by laminin and fibronectin. Collagen type-IV stimulated only cell migration of U-251/lacZ cells. Scanning electron microscopy revealed an extensive change in cell shape as a result of laminin stimulation. Flowcytometric studies showed that both AN1/lacZ and U-251/lacZ strongly express the alpha3 beta1 integrin receptor, which can bind to several ECM components (laminin, fibronectin, collagen). Immunofluorescence microscopy demonstrated that the same integrin sub-units were expressed in multicellular spheroids. When monoclonal antibodies to alpha3 and beta1 were added to the laminin-stimulated cultures, cell migration was significantly reduced. This indicates that the alpha3 beta1 integrin receptor plays an important role during glioma-cell migration.
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PMID:Stimulation of glioma-cell migration by laminin and inhibition by anti-alpha3 and anti-beta1 integrin antibodies. 882 48

Gliomas exhibit diffuse infiltration into the normal brain parenchyma, and the tumor cells often show morphological features similar to reactive glia cells, making it difficult to discriminate tumor cells from other neural cell populations both in vitro and in vivo. Several methods have therefore been developed in order to observe migrating tumor cells in experimental tumor models. These include labeling of tumor cells with vital dyes as well as by using genetic markers. Despite the fact that these malignancies are highly invasive in the brain, they rarely metastazise out of the central nervous system (CNS). The dissemination of tumor cells is probably mediated both by passive cell displacement and by active cell migration. Tumor cells may be displaced within the brain by the passive flow of cerebrospinal fluid (CSF) within the perivascular space and along ventricular linings. Tumor growth and invasion occur in a micromillieu that is regulated both by cancer cells and normal cells. The biological attributes of invasion and cell migration include cell adhesion to extracellular matrix components, cell locomotion, and the ability to create space into which to move. This process is characterized by the degradation and turnover of ECM components, which implies the production of specific proteases and inhibitors. Tumor progression is also influenced by numerous growth factors which may stimulate the malignant cells both by paracrine and autocrine mechanisms. Tumor growth requires the persistent formation of new blood vessels and the induction of angiogenesis is most likely occurring during early stages of tumor development. This process is regulated both by several inducers and inhibitors of endothelial cell proliferation and migration.
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PMID:Brain tumor cell invasion, anatomical and biological considerations. 942 45

Within the brain, dissemination of glioma cells follows myelinated fiber tracts and extracellular matrix containing structures such as the basement membranes of blood vessels. These patterns represent the two major routes of invasion frequently observed in clinical disease. Previously, we have characterized the substrates for preferential glioma adhesion and migration on purified ECM protein. In this study sections of human brain from different anatomical regions were used as adhesive substrates and also characterized for the presence and distribution of matrix proteins. Adhesion of marker gene transfected glioma cell suspensions to different regions and anatomical structures of human brain was quantified using a computer assisted image analysis system. Monoclonal antibodies against different adhesion molecules were used to inhibit glioma cell attachment ot specific anatomical structures. In addition, glioma cell aggregates were allowed to adhere to brain sections and single cells were observed to migrate out of these aggregates. Scanning electron microscopy was used to morphologically study the preferred routes of glioma dissemination on brain sections. In brain sections different kinetics of cell adhesion to distinct structures were observed. Within 15 minutes cells adhered and spread on blood vessels and arachnoid tissue containing sections. Choroid plexus and the ventricular wall were also adhesive structures. Adhesion to cortex required 1 hour, while adhesion and spreading on myelinated fiber tracts was retarded and required several hours of incubation. The predominant matrix proteins in small vessels were found to be laminin, collagen type IV, and fibronectin. Choroid plexus and the ependyma showed a similar composition of matrix proteins. Arachnoid fibers contained different types of collagens, predominately type I and III, whereas the only matrix protein identified in the subependyma was fibronectin. Antibodies to the alpha 2, alpha 3, and beta 1 integrin subunits completely blocked adhesion to arachnoid tissue, anti-NCAM inhibited attachment to cortex. Adhesion to blood vessels in brain sections could only be inhibited to 50% by anti-integrin beta 1. Antibodies to the av containing integrin av beta 3 also blocked 50% of adhesion to vessels. Our findings indicate that adhesion of glioma cells to brain sections most rapidly takes place on ECM protein containing regions, especially blood vessels which may serve as guiding structures for glioma dissemination.
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PMID:Glioma cell adhesion and migration on human brain sections. 970 90

Cell adhesion receptors of the integrin superfamily, CD44, and adhesion receptors of the immunoglobulin superfamily are expressed by high-grade astrocytic tumors of the central nervous system. These receptors are critical for the invasion of these tumors in the nervous system. Glioma cells utilize these receptors to adhere to and migrate along the components of the extracellular matrix, which is uniquely distributed and regulated within the brain and the spinal cord. For this reason, glioma cell invasion into the adjacent brain tissue is dependent on the interaction of glioma cells with the extracellular matrix. The receptor-ECM component interaction is discussed, focusing on the role of cell adhesion molecules of the integrin family and CD44 in glioma cell adhesion and invasion.
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PMID:ECM-mediated glioma cell invasion. 984 Aug 3

The aim of the study was to assess the differential intra- and intertumoral heterogeneity and patterns of matrix metalloproteinase expression in human glioblastomas in vivo. 12 glioblastoma samples were analyzed for MMP expression by semi-quantitative RT-PCR. A total of 56 samples (8 adjoining regions of 6 glioblastoma tumors) were immunohistochemically examined for the expression and regional distribution of gelatinase-A (MMP-2), gelatinase-B (MMP-9), matrilysin (MMP-7) and stromelysin-1 (MMP-3). Gelatinase-A mRNA was detected in all samples, gelatinase-B was found in numerous samples. Correspondingly, strong expression levels of both gelatinase protein was seen in immunohistochemistry. Gelatinase-A was expressed by both tumor cells and endothelium while gelatinase-B was found to be restricted to endothelial cells. Stromelysin-1 protein was not detected in any of the samples. Matrilysin was found around tumor cells of three samples from one patient only. The strong immunoreactivity seen for gelatinase-A around tumor cells and blood vessels suggests a role in both tissue degradation and tumor neoangiogenesis which is in accordance with previously published in vitro data. The marked localization of gelatinase-B to the endothelium and its presence in non-infiltrative benign lesions, however, makes a direct proteolytic role of gelatinase-B on ECM components during glioma invasion appear unlikely. Its close association with vascular structures, however, might indicate a link to neoangiogenesis. The significance of matrilysin which was only seen in tumor cells in three samples remains unclear. Stromelysin-1, though strongly expressed in cell lines, does not appear to play a role in glioblastoma tumors in vivo.
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PMID:Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas. 1057 6

Aims of the study were: 1. to establish the prevalence of CD44 protein expression in human astrocytomas; 2. to compare the distribution of the extracellular matrix in these tumors; 3. to investigate the relation between CD 44, the extracellular matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were detected by immunohistochemistry in formalin fixed paraffin embedded tissue samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9 of 35 GB (25.7%) showed LN positivity. There was a negative correlation between LN expression and tumor grade (p=0.03). FN was either localized in the basement membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN distribution was not uniform and its staining intensity showed decrease in GB. 3A (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in some tumor cells of 19 GBs. TN expression was positively correlated with the degree of vascular endothelial proliferation in GB (p<0.05). The expression of CD44s wasseen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3 of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite strong especially near the vessels. There was a good correlation between TN and CD44s expression in human astrocytic tumors (p=0.005). No relationship was observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN expression showed increase with malignancy in astrocytomas. These findings indicated that the histological malignancy of the astrocytomas was correlated with expression of TN and CD44s. It was suggested that in astrocytomas there was a biological relationship only between CD44 and TN, but none with the other ECM proteins. TN may play a role in angiogenesis in human astrocytic tumors.
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PMID:The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas. 1093 87

Cell invasion requires cooperation between adhesion receptors and matrix metalloproteinases (MMPs). Membrane type (MT)-MMPs have been thought to be primarily involved in the breakdown of the extracellular matrix. Our report presents evidence that MT-MMPs in addition to the breakdown of the extracellular matrix may be engaged in proteolysis of adhesion receptors on tumor cell surfaces. Overexpression of MT1-MMP by glioma and fibrosarcoma cells led to proteolytic degradation of cell surface tissue transglutaminase (tTG) at the leading edge of motile cancer cells. In agreement, structurally related MT1-MMP, MT2-MMP, and MT3-MMP but not evolutionary distant MT4-MMP efficiently degraded purified tTG in vitro. Because cell surface tTG represents a ubiquitously expressed, potent integrin-binding adhesion coreceptor involved in the binding of cells to fibronectin (Fn), the proteolytic degradation of tTG by MT1-MMP specifically suppressed cell adhesion and migration on Fn. Reciprocally, Fn in vitro and in cultured cells protected its surface receptor, tTG, from proteolysis by MT1-MMP, thereby supporting cell adhesion and locomotion. In contrast, the proteolytic degradation of tTG stimulated migration of cells on collagen matrices. Together, our observations suggest both an important coreceptor role for cell surface tTG and a novel regulatory function of membrane-anchored MMPs in cancer cell adhesion and locomotion. Proteolysis of adhesion proteins colocalized with MT-MMPs at discrete regions on the surface of migrating tumor cells might be controlled by composition of the surrounding ECM.
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PMID:Matrix-dependent proteolysis of surface transglutaminase by membrane-type metalloproteinase regulates cancer cell adhesion and locomotion. 1127 23


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