Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laminin and fibronectin, the major noncollagenous matrix glycoproteins, were studied in connection with normal brain cells and neuroectodermal cell lines. Laminin, a Mr 900,000 dalton matrix glycoprotein and an essential component of basement membranes, was found to be produced by cultured cells of several malignant cell lines of neuroectodermal origin. In cultured mouse C1300 neuroblastoma line cells laminin was localized, by immunoelectron microscopy, to the rough endoplasmic reticulum and, to sites of cell-to-cell and cell-to-substratum adhesion. Further experiments on the intracellular transport of this glycoprotein in C1300 cells confirmed that laminin is, at least partially, transported through the Golgi pathway. These results favor a role for laminin in attachment and cellular interactions of malignant neuronal cells. Laminin was also found in connection with neurons and glial cells from mammalian brain. In primary cultures from developing rat brain the vast majority of non-neuronal cells (80%) expressed immunoreactivity for the glial fibrillary acidic protein, a cytoskeletal protein specific for astrocytes. During the first week in culture all the glial fibrillary acidic protein-positive cells, with the exception of mature-looking star-shaped astrocytes, exhibited immunoreactivity for laminin. The intracellular laminin disappeared gradually after a few weeks in culture, but an extensive laminin matrix persisted and seemed to be localized on the upper surface of the non-neuronal cells. The neurofilament-positive neurons were negative for laminin. Pretreatment of the cultures with the ionophore monensin, caused accumulation of laminin-immunoreactivity within the Golgi region, which confirmed that laminin is, indeed, produced by cultured astrocytes and secreted through the Golgi complex. No fibronectin immunoreactivity was found in the majority of glial cells. However, under culture conditions where fibronectin was omitted from the culture medium there was, in the primary cultures, a minor population of glial fibrillary acidic protein-positive flat glial cells that exhibited intracytoplasmic immunofluorescence for fibronectin. In the presence of fibronectin in culture medium no fibronectin-positive glial cells could be detected. It thus appears that laminin, and to a minor extent fibronectin, are proteins that normal glial cells are capable of producing under specific conditions. Laminin and fibronectin were localized in adult rat brain in capillary and meningeal structures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Laminin and fibronectin in normal and malignant neuroectodermal cells. 638 23

The differential adhesion of cultured mammalian clonal cell lines to components of the extracellular matrix was examined by kinetic adhesion and long-term growth assays. Uniform artificial matrices were prepared by air drying collagen Type I solution (C) onto a microtiter well and then air drying a solution containing a single glycosaminoglycan (GAG): hyaluronic acid (HA), chondroitin sulfate-4 (CHS-4), or chondroitin sulfate-6 (CHS-6). The adhesion of [3H]thymidine-prelabeled cells suspended in fibronectin (FN) depleted medium was measured at 2 and 6 hr. Neuroblastoma (N18, Lan 1) and melanoma (B16, G361, S91) cell lines exhibited a significantly greater percentage of cells adhering to one or more C-GAG matrices compared with C matrices. Maximal adhesion at 2 hr was to C-HA. In contrast at 2 hr, two glial, two epithelial, and one fibroblastic cell line showed unchanged or significantly decreased binding to C-GAG compared with C matrices. Further experiments using a neuroblastoma (N18) and a glioma (C6) cell line indicated that the adhesion patterns were not altered either by the method of dissociation from the tissue culture dish, preincubation with exogenous GAG, or the addition of exogenous fibronectin. Assays of N18 and C6 adhesion to matrices made from a non-GAG polyanionic compound, polygalacturonic acid (PGA), did not yield the same adhesion patterns as C-HA matrices. Long-term growth studies of a neuroblastoma (N18) melanoma (S91), and glioma (C6) cell line on nonuniform matrices deliberately prepared with GAG-rich and GAG-poor regions complemented the observations from the kinetic adhesion assays. N18 and S91 cells did not grow on areas which did not contain GAG by toluidine blue staining. However, the C6 cells did not grow on areas which did strongly stain for GAG. A quantitative analysis of the long term growth of N18 and C6 cells substantiated these observations. All these data indicate that the cellular phenotype may be correlated with matrix adhesion. Neuroblastomas and melanomas have a greater affinity for GAG-containing matrices while glial, epithelial, and fibroblastic cells appear to have a greater or equal affinity for collagen matrices.
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PMID:Correlation of the cell phenotype of cultured cell lines with their adhesion to components of the extracellular matrix. 640 96

A method using proteins covalently coupled to glass surfaces has been applied to studies on the differentiation of neuroblasts. Neuroblastoma cells from clones N 18 and NIE 115 adhere to surfaces coated with fibronectin or laminin and extend rapidly growth cone-containing neurites. Some lectin-coated surfaces are also able to support neurite outgrowth, although the activities are lower than those of fibronectin and laminin. We discuss the biochemical requirements of the surface structures capable of inducing a differentiated neuronal morphology to neuroblastoma cells, and also consider the possible relationship of the results to physiological differentiation phenomena.
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PMID:Neurite outgrowth of neuroblastoma cells induced by proteins covalently coupled to glass coverslips. 648 60

Neurite outgrowth of C 1300 neuroblastoma cells, which were dispersed from adherent cultures or grown in suspension, was studied on different protein-coated surfaces. Of 29 different surface structures studied, including surfaces treated with various fibronectins, lectins, glycosidases, or glycosyltransferases capable of stimulating fibroblast spreading, only the surfaces coated with plasma fibronectin or with a protein mixture secreted by C6 glioma cells displayed an extensive activity in the sprouting assay. Neurite outgrowth was inhibited by brain gangliosides and by colominic acid (a sialic acid polymer). A 50% inhibition of neurite outgrowth of N18 neuroblasts induced by the glioma cell proteins was observed at the following approximate concentration: 100 microM (0.2 mg/ml) GD1A ganglioside, 20 microM (0.04 mg/ml) GT1B ganglioside, and 5 mg/ml colominic acid. Specificity of inhibition was suggested by the finding that a few polyanionic substances tested were not inhibitory in the sprouting assay, and that the type of gangliosides inhibiting sprouting were found to be major sialoglycolipids of the neuroblasts. A hypothesis is discussed, according to which neurite outgrowth of neuroblasts is stimulated by adhesion involving interactions of the adhesion-mediating protein with cell surface carbohydrates characteristic of brain gangliosides.
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PMID:Neurite outgrowth of neuroblastoma cells: dependence on adhesion surface--cell surface interactions. 669 78

The monoclonal antibody UJ 127-11 was raised following immunization of mice with human foetal brain and subsequent somatic cell hybridization of spleen cells with the mouse myeloma cell line P3-X63-Ag8-653. Studies on normal foetal and adult tissues show that, by indirect immunofluorescence, the antigen recognized by UJ 127:11 is restricted in its expression to cells of neural rather than glial origin. Neural tumours such as neuroblastoma, medulloblastoma and ganglioglioma (neural component) bind the monoclonal antibody whereas malignancies originating from glial cells do not bind UJ 127:11. Biochemically the monoclonal antibody has been shown to bind to a glycoprotein of 220,000-240,000 mol. wt. under reducing and non-reducing conditions. Despite similarities in the molecular weight between human fibronectin and the antigen recognized by UJ 127:11, they have different serological and biochemical characteristics, suggesting that the monoclonal antibody is not binding to either cell or plasma fibronectin.
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PMID:Monoclonal antibody UJ 127:11 detects a 220,000-240,000 kdal. glycoprotein present on a sub-set of neuroectodermally derived cells. 682 47

Both polyvalent and hybridoma-produced antibodies to fibronectin (Fn) were used to 'map' the immunoaccessible subsets of cell surface fibronectin on virus-transformed murine fibroblast SVT2 and rat neuroblastoma B104 cells. As one approach to this end, attachment and spreading responses of cells were measured on tissue culture substrata coated with antibody or with plasma fibronectin to compare their adhesive responses. Both SVT2 and B104 cells adhere poorly to polyvalent anti-Fn-coated substrata over short time intervals, but within several hours changes occur which permit cells to attach and spread as well on anti-Fn as on Fn (post-adsorption of the anti-Fn with Fn also generates a maximal response). This adhesive response could be completely prevented by predigesting the cells with Flavobacterium heparanase, but not with chondroitinase ABC, indicating that the cell surface Fn responsible for antibody-mediated adhesion is associated with heparan sulfate proteoglycans on the cell surface. The compositions of the substratum-attached material (left bound after EGTA-mediated detachment of cells) from cells attaching to anti-Fn or Fn were analysed by SDS-PAGE and found to be identical within the same cell type for the two different substrata. Three hybridoma-produced antibodies, which recognize different determinants on Fn, generated different adhesive responses for SVT2 or B104 cells when adsorbed to the substratum. SVT2 cells adhered well to antibody no. 32-coated substrata but poorly to antibodies 92 or 136; on the other hand, B104 cells responded similarly to all three antibodies over short times of attachment but much better to no. 32 after a several hour incubation. These experiments indicate that (1) much of the cell surface fibronectin is complexed with heparan sulfate proteoglycan and is initially inaccessible to bind to polyvalent antibody on the substratum to promote adhesion; (2) the surface of neuroblastoma cells contains a fibronectin-like molecule which is important in their substratum adhesion; and (3) monoclonal antibodies are valuable tools in 'mapping' the orientation of cell surface molecules like fibronectin by measuring adhesive responses to antibody-coated substrata.
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PMID:Adhesive responses of fibroblast and neuroblastoma cells to substrata coated with polyvalent or monoclonal antibody to fibronectin. 686 9

The deposition of the basement membrane glycoproteins, laminin, fibronectin, and type IV procollagen was studied by indirect immunofluorescence microscopy during the attachment and differentiation of murine C-1300 neuroblastoma cells. A typical cytoplasmic perinuclear staining for the basement membrane antigens was seen both in undifferentiated and differentiated cells. Freshly seeded suspended cells lacked surface fluorescence but in two hours after plating, distinct punctate laminin deposits became discernible on the ventral surface of the cells. Notably, in sparsely seeded undifferentiated cultures, the cell-associated extracellular laminin deposits could only be detected under the primary attaching cells, whereas daughter cells in clonal cell colonies lacked such fluorescence. In cultures induced to neurite formation with dibutyryl cyclic AMP, laminin deposition was also detected in association with the growing cytoplasmic extensions. No distinct differences were found between the secreted proteins of cultures of differentiated and nondifferentiated neuroblastoma cells, but the patterns of fucosylation of high-molecular weight proteins in the two cultures were markedly different. We conclude that cultured neuroblastoma cells both synthesize, secrete and deposit laminin. The distribution of laminin during neuroblastoma cell attachment and neurite extension suggests that this glycoprotein may be involved in cell-to-substratum interactions in C-1300 cell cultures.
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PMID:Deposition of basement membrane proteins in attachment and neurite formation of cultured murine C-1300 neuroblastoma cells. 706 77

Murine neuroblastoma cells have been widely used as a model system for neuronal cells as they can be induced to differentiate in culture by various stimuli, such as dibutyryl cyclic AMP (dbcAMP), prostaglandin, and serum starvation. The cells respond with assembly of microtubules, leading to neurite outgrowth, with increased activity of neuronal-specific enzymes, tyrosine hydroxylase, choline acetyltransferase and acetylcholine-esterase, and synthesis of neurotransmitters. The differentiated cells lose tumorigenicity. Cell-to-substratum adhesion is evidently crucial for neurone extension in vitro. Neurite outgrowth is induced by treatments that increase cell-to-substratum adhesion in some neuronal cell cultures. We have now identified the major high molecular weight proteins synthesized and secreted by murine C1300 neuroblastoma cells as fibronectin, laminin and type IV procollagen, of which the latter two were also found to be deposited in pericellular matrix form.
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PMID:Basal lamina glycoproteins are produced by neuroblastoma cells. 743 74

We previously identified a human cDNA encoding a novel receptor tyrosine kinase, termed Sky, which is predominantly expressed in the brain and has a unique extracellular domain consisting of two immunoglobulin (Ig)-like and two fibronectin type III (FN III) motifs. In attempts to define the functional role of the Sky receptor, we cloned a rat sky cDNA, and localized the sites of expression of sky transcript in the adult rat brain by Northern blot and in situ hybridization analyses using the cloned rat cDNA as a probe. The deduced amino acid sequence of rat Sky has an overall sequence and a domain topology highly conserved with human Sky (90% overall identity and 98% identity within the tyrosine kinase domain). Northern blot analysis revealed that a single 3.8-kb sky mRNA is expressed in PC12 pheochromocytoma and Neuro-2a neuroblastoma cell lines and in various regions of the adult rat brain. In situ hybridization analysis revealed widespread but confined neuronal populations in adult rat brain that express sky transcript; prominent hybridization signals were detected in the inner granular layer of the olfactory bulb, CA-1 area of the hippocampus, granule cell layer of the cerebellum, tenia tectum and cingulate gyrus neurons, and wide regions of cortex layers II-VI. The high level of expression of sky mRNA in neurons in restricted brain regions suggests that the Sky receptor may play an important role in development, function, and maintenance of specific neuronal populations in the central nervous system.
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PMID:Molecular cloning and in situ localization in the brain of rat sky receptor tyrosine kinase. 749 Feb 70

Cell-adhesion activity of the bovine propolypeptide of von Willebrand factor (pp-vWF) was assessed by means of an in vitro assay with several cell lines of both normal and tumor-cell origin. pp-vWF promoted adhesion and spreading of B16 mouse melanoma cells and G-361 human melanoma cells. However, it could not induce adhesion of any other cell lines tested including endothelial cells, normal fibroblasts, and tumor cells of sarcoma, carcinoma, neuroblastoma and leukemia origin. A monospecific polyclonal antibody against pp-vWF, but not against fibronectin, laminin, and von Willebrand factor (vWF), completely blocked the pp-vWF-mediated adhesion, indicating that the cell adhesion was due to the pp-vWF molecule and not due to possible contamination of these three well-known adhesive proteins. The cell-adhesion activity was also observed with human pp-vWF and, furthermore, the adhesion to both bovine and human pp-vWF was not affected by a peptide containing the Arg-Gly-Asp sequence while the peptide abolished the cell adhesion to vWF. The adhesion was completely dependent on Mg2+ and inhibited by Ca2+. Inhibition by an anti-(beta 1 integrin) mAb (4B4) indicates that the receptor for this protein belongs to the beta 1-integrin family. A monoclonal antibody (TC4) among several antibodies directed against bovine pp-vWF inhibited the B16 adhesion to immobilized pp-vWF. The epitope for this monoclonal antibody lies in a central 8-kDa portion of pp-vWF, suggesting that this region is important for the cell-adhesion activity. This idea was supported by the finding that purified 8-kDa fragment promoted adhesion of B16 cells in a concentration-dependent manner. As pp-vWF shows unique cell-type specificity in its adhesion activity, which is completely different from that of fibronectin, laminin, vWF and collagen, it may be a novel type of adhesive glycoprotein that utilizes a beta 1-integrin receptor.
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PMID:Beta 1-integrin-mediated adhesion of melanoma cells to the propolypeptide of von Willebrand factor. 751 67


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