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)

The large cytoplasmic domain form of the neural cell adhesion molecule N-CAM has been reported to interact specifically with fodrin, a submembranous cytoskeletal protein. We tested the abilities of fodrins from bovine brain and embryonic chicken brain to bind to N-CAM that had been isolated from differentiated or undifferentiated mouse N2A neuroblastoma cells or from the brains of embryonic day 11 or day 14 chickens. Labeled fodrin samples bound with immobilized fodrin at a minimum soluble fodrin concentration of 2.5 x 10(-8) M, but the labeled fodrin did not bind to the immobilized N-CAM when incubated at 20-fold higher fodrin concentrations.
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PMID:Solid-phase binding analysis of N-CAM interactions with brain fodrin. 815 73

The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.
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PMID:Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins. 827 80

We examined the localization of the 140- and 180-kDa transmembrane isoforms of chicken N-CAM following transfection into mouse N2A neuroblastoma cells. Both isoforms were expressed at the cell surface and became partially or completely localized at areas of cell-cell contact after several days of culture or of in vitro differentiation. These results indicate that the presence of the large cytoplasmic domain of the 180-kDa N-CAM isoform is not necessary to bring about the localization of N-CAM to points of cell-cell contact.
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PMID:The large cytoplasmic domain is not required for concentration of N-CAM at cell-cell contacts in transfected mouse neuroblastoma cells. 848 39

We previously cloned cDNAs encoding two different polysialic acid (PSA) synthases, ST8Sia II and IV, from mouse, and showed that both mouse ST8Sia II and IV can synthesize PSA on the neural cell adhesion molecule (NCAM) as well as other glycoproteins such as fetuin, at least in vitro (Kojima, N., Tachida, Y., Yoshida, Y., and Tsuji, S. (1996) J. Biol. Chem. 271, 19457-19463]. In the present study, to clarify how the two PSA synthases act differently in vivo, we first cloned PSA-expressing cell lines (N2a-II and N2a-IV) by stable transfection of the cDNA encoding either mST8Sia II or IV into mouse neuroblastoma Neuro2a cells, which do not express PSA but express NCAM, then compared the expression of the PSA and NCAM isoforms and de novo synthesis of PSA between N2a-II and N2a-IV. Western blotting with an anti-NCAM polyclonal antibody showed that NCAM was expressed as the polysialylated form in both ST8Sia II cDNA-transfected and ST8Sia IV cDNA-transfected Neuro2a cells, but that the polysialylated NCAMs expressed in ST8Sia IV cDNA-transfected clones migrated much slower on SDS-PAGE than those expressed in ST8Sia II cDNA-transfected clones. The slower migration of polysialylated NCAM of the ST8Sia IV cDNA-transfected clone (N2a-IV) than that of the ST8Sia II cDNA-transfected clone (N2a-II) was also observed when cells were metabolically labeled with [3H]glucosamine or pulse-chase labeled with [35S] methionine followed by immunoprecipitation with anti-PSA antibody or anti-NCAM monoclonal antibody. In addition, polysialylated N-glycans of PSA-carrying glycoproteins prepared from [3H] glucosamine-labeled N2a-IV by immunoprecipitation with anti-PSA monoclonal antibody were eluted at a much higher salt concentration than those from [3H] glucosamine-labeled N2a-II on an anion-exchange column. These results indicated that the degree of de novo polysialylation of NCAM by mST8Sia IV was much higher than that by mST8Sia II. In N2a-IV, NCAM-120, -140, and -180 were expressed as polysialylated forms, while polysialylation was restricted to NCAM-140 and -180, i.e., not NCAM-120, in N2a-ST8Sia II. Metabolic labeling of the cells with [3H] glucosamine, pulse-chase labeling with [35S] methionine followed by immunoprecipitation with anti-PSA antibody, and subsequent sialidase treatment revealed that NCAM-140 and -180 were specifically polysialylated in N2a-II, whereas not only NCAM but also other glycoproteins were de novo polysialylated in N2a-IV. The above results demonstrated that the two different PSA synthases, mST8Sia II and IV, synthesize PSA of different lengths on different substrate glycoproteins in vivo when the enzymes are expressed in neuroblastoma Neuro2a cells. These differences suggest that mST8Sia II and IV play different roles in the biosynthesis and expression of PSA.
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PMID:Two polysialic acid synthases, mouse ST8Sia II and IV, synthesize different degrees of polysialic acids on different substrate glycoproteins in mouse neuroblastoma Neuro2a cells. 949 75

A mounting body of evidence suggests that cell adhesion molecules (CAMs) play important roles in morphogenetic patterning of the nervous system. The combined factors that control the expression of CAMs during early neural development are, however, largely unknown. We have hypothesized that the coordinate expression of homeobox (Hox) and paired box (Pax) proteins in the neural axis leads to the differential expression of particular CAM genes. Following this hypothesis, we have characterized the promoters and identified cis-regulatory sequences that bind to and respond to Hox and Pax proteins in the genes for three neurally expressed CAMs - the neural cell adhesion molecule, N-CAM, the neuron-glia cell adhesion molecule, Ng-CAM, and L1. Experiments on transgenic mice carrying N-CAM promoter/lacZ reporter gene constructs indicated that mutation of either the HBS or the PBS disrupted patterning of N-CAM expression in the embryonic spinal cord. To examine the factors that restrict the expression of certain CAMs to the nervous system, we identified regulatory elements that block expression of the Ng-CAM and L1 genes in non-neural cells. We characterized a 310 base pair region of the first intron of the Ng-CAM gene containing five neural restrictive silencer elements (NRSEs) and a binding site for the Pax-3 protein. These elements silenced activity of the Ng-CAM promoter in NIH3T3 fibroblasts, but had no effect on its activity in N2A neuroblastoma cells line. Similar analyses of the L1 gene revealed a single NRSE within the second intron that was important for silencing in this cellular transfection system. To analyze the role of the NRSE in vivo, we prepared transgenic mice containing two L1 gene/lacZ constructs, one containing the NRSE and another in which the NRSE was deleted. The wild type L1lacZ transgene showed a neurally restricted pattern of expression, whereas the NRSE-mutated L1 construct showed extensive extraneural expression of the L1 gene. Thus, neural specificity of CAM expression is controlled by the NRSE. The general significance of these observations is that they connect the expression of important families of transcriptional regulators with gene products capable of direct cellular mechanochemistry.
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PMID:Gene regulation of cell adhesion: a key step in neural morphogenesis. 965 50

The function of the neural cell adhesion molecule, NCAM, is modulated by the expression of the N-linked polysialic acid (PSA) oligosaccharide chain, with PSA serving to decrease the adhesive potential of the protein backbone. In this study, we have generated clonal cells of the rat B104 and human SH-SY5Y neuroblastoma cell lines that over-express the alpha2,6(N) sialyltransferase (ST6N) enzyme in order to investigate the role of this enzyme in PSA biosynthesis. The clonal cells exhibited ST enzyme activities of up to 20-times control levels, which remained stable throughout the duration of the study. The increase in enzyme activity paralleled an increase in enzyme protein levels, as determined by Western blot analysis, and immunocytochemical analysis confirmed the Golgi localisation of the enzyme. The induction of PSA-NCAM expression in the cells expressing high levels of ST6N was confirmed both by using anti-PSA antisera and by specific digestion with endo-N-acetylneuraminidase E, whose actions are specific for alpha2, 8-linked PSA chains. These results demonstrate that the cellular ST6N activity serves to positively influence the expression of PSA in neuronal cells.
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PMID:Overexpression of the alpha2,6 (N) sialyltransferase enzyme in human and rat neural cell lines is associated with increased expression of the polysialic acid epitope. 1056 92

The subcommissural organ (SCO) is a specialized ependymal structure of the brain that secretes glycoproteins into the cerebrospinal fluid (CSF), which condense to form a thread-like structure - Reissner's fiber (RF). The effects of soluble material released by RF were examined on neuroblastoma B104 cells grown in serum-free medium, using "low-density" and "high-density" culture systems. In the presence of soluble RF material, low-density cultures were suitable for analysis of the enhanced neurite outgrowth of B104 cells, while high-density cultures allowed the increased B104 cell aggregation to be examined. RF-induced neuronal aggregation and neuritic outgrowth were restricted to a perimeter around the RF. This standardized cell culture system reproduced in part the effects observed previously with primary cortical and spinal cord cell cultures and may serve the analysis of the mechanisms leading to aggregation and neurite outgrowth. In the present study, we analyzed variations in the rate of neural cell adhesion molecules, such as N-CAM and N-cadherin, induced by soluble RF material in high-density cultures.
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PMID:Neuroblastoma B104 cell line as a model for analysis of neurite outgrowth and neuronal aggregation induced by Reissner's fiber material. 1057 Nov 12

Metastatic stage IV neuroblastoma tumors, as well as cell lines derived from them, are highly malignant and rapidly fatal. To determine whether malignant potential of these cells might be influenced by stromal tissue at sites frequently involved in metastasis, we initiated primary cultures from bone marrow of three patients (331, 337, and 91) with stage IV neuroblastoma. All three explants contained two distinct cell populations, malignant neuroblasts (Nb-type) and substrate adherent stromal-like (Str-type) cells. The cell types were separated at the first passage and studied by cytogenetic, molecular, and immunocytochemical methods. Karyotypic analyses after 3-6 passages in vitro revealed the presence of unique chromosomal abnormalities in Nb-type cells of all three lines: (1) der(1)t(1;7) (p32;q11) and der(5)t(5;17)(q35;q21) in pseudodiploid IGR-N-331 neuroblasts; (2) der(1)t(1;17)(p35;q21-22) x 2 and der(7)t(7;7)(p21;q21) in IGR-N-337 hyperdiploid neuroblasts; and (3) more than six rearranged chromosomes in two related subpopulations of hypodiploid IGR-N-91 neuroblasts. Neuroblastic cells from all three tumors amplified MYCN 25- to 50-fold (with amplified genes visible as dmin or, in one IGR-N-91 subline, as an hsr(14)[q32]) and expressed N-CAM. Str-type cells from tumors 331 and 337 had a normal diploid karyotype, did not express either N-CAM or S-100, and are probably normal bone marrow fibroblasts. By contrast, S-100 negative Str-type IGR-N-91 cells were hypodiploid and shared at least two unbalanced translocations, der(4)t(1;4)(q12;p15) and der(2)t(2;10;17)(p14;q11;q22), with neuroblastic counterparts, indicating that "stromal" cells and malignant neuroblasts had a common tumor cell origin. Thus, the Str-type cells of IGR-N-91 are examples of S-type phenotypic variants frequently described for long-term human neuroblastoma cells lines in vitro, but not previously observed in vivo.
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PMID:Phenotypic and genotypic diversity of human neuroblastoma studied in three IGR cell line models derived from bone marrow metastases. 1068 38

Cell-adhesion molecules are thought to play crucial roles in development and plasticity in the nervous system. Four neural cell adhesion molecules CD9, CD24, L1 and N-CAM are associated in the surface membrane of cultured neuroblastoma cells as studied by chemical cross-linking with bifunctional reagent 3,3'-dithiobis (sulphosuccinimidyl-propionate) followed by a subsequent immunodetection using antibodies directed against the above molecules. We obtained direct evidence of CD9 and L1, but not CD9 and N-CAM clasterisation, also interactions of CD24 with L1, CD24 with N-CAM and some others. These observations illustrate topography of neural cell adhesion molecules located in the vicinity to each other and imply the basis for their functional cooperativity.
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PMID:[Topography of cell ahesion molecules CD9, CD24, L1 and N-CAM on the surface of neuroblastoma cells studied using chemical cross linking]. 1084 35

Cell adhesion molecules (CAM) represent a large group of cell surface protein moieties with distinctive biological functions. In physiological terms they ascertain cell to cell contact such as cell cohesion of epithelia, condition cell migration and transmigration via biological membranes such as blood vessel walls, provide means for homing cells in a new microenvironment etc. These features of CAM are exploited by tumor cells to grow and spread in a tumor bearing host. CD56/N-CAM antigen is 140 kD isoform of neural cell adhesion molecule. N-CAM belongs to the large Ig superfamily of CAMs. CD56 can be traced at various sites, including nervous tissue, neuro-muscular junctions, neuroendocrine and endocrine organs. It is well known as a differentiation antigen of natural killer (NK) cells. Its role and function are far from clear, but its adhesion properties are evident in cell-cell (homophilic) interactions. CD56 has been, however, demonstrated the cells various human malignancies. Tumors of the nervous system such as neuroblastoma, are well known to express this marker. Malignant lymphomas of T-NK cell origin bear CD56, as well as multiple myeloma, melanoma and some cancers of epithelial origin. These data suggest that CD56/N-CAM antigen is, in some unknown manner involved in tumor biology.
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PMID:Significance of cell adhesion molecules, CD56/NCAM in particular, in human tumor growth and spreading. 1182 Jun 19


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