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)

Previous studies have shown that the BM88 antigen, a neuron-specific molecule, promotes the differentiation of mouse neuroblastoma cells [23] (Mamalaki A., Boutou E., Hurel C., Patsavoudi E., Tzartos S. and Matsas R. (1995) The BM88 antigen, a novel neuron-specific molecule, enhances the differentiation of mouse neuroblastoma cells. J. Biol. Chem. 270, 14201-14208). In particular, stably transfected with the BM88 cDNA, Neuro 2a cells over-expressing the BM88 antigen are morphologically distinct from their non-transfected counterparts; they exhibit enhanced process outgrowth and a slower rate of division. Moreover, they respond differentially to growth factors [10] (Gomez J., Boutou E., Hurel C., Mamalaki A., Kentroti S. , Vernadakis A. and Matsas R. (1998) Overexpression of the neuron-specific molecule BM88 in mouse neuroblastoma cells: Altered responsiveness to growth factors. J. Neurosci. Res. 51, 119-128). In order to further elucidate the role of the BM88 antigen in the differentiation of developing neurons we used the in vitro system of differentiating P19 cells which closely resembles early murine development in vivo. In this study, P19 cells were driven to the neuronal pathway with retinoic acid. We examined by immunofluorescence studies the expression of the BM88 antigen in these cells and we found that it correlates well with the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) which characterizes early differentiating post-mitotic neurons. In contrast, very few of the BM88 antigen-positive/PSA-NCAM-positive cells expressed neurofilament protein, a marker of more mature neurons. Our findings, in accordance with previously reported data, strongly suggest that the BM88 antigen is involved in the early stages of differentiation of neuronal cells.
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PMID:Early expression of the BM88 antigen during neuronal differentiation of P19 embryonal carcinoma cells. 1071 87

Increasing evidence suggests that alcohols act within specific binding pockets of selective neural proteins; however, antagonists at these sites have not been identified. 1-Alcohols from methanol through 1-butanol inhibit with increasing potency the cell-cell adhesion mediated by the immunoglobulin cell adhesion molecule L1. An abrupt cutoff exists after 1-butanol, with 1-pentanol and higher 1-alcohols showing no effect. Here, we demonstrate surprisingly strict structural requirements for alcohol inhibition of cell-cell adhesion in L1-transfected NIH 3T3 fibroblasts and in NG108-15 neuroblastoma x glioma hybrid cells treated with BMP-7, an inducer of L1 and neural cell adhesion molecule. The target site discriminates the tertiary structure of straight-chain and branched-chain alcohols and appears to comprise both a hydrophobic binding site and an adjacent hydrophilic allosteric site. Modifications to the 2- and 3-carbon positions of 1-butanol increased potency, whereas modifications that restrict movement about the 4-carbon abolished activity. The effects of ethanol and 1-butanol on cell-cell adhesion were antagonized by 1-pentanol (IC(50) = 715 microM) and 1-octanol (IC(50) = 3.6 microM). Antagonism by 1-octanol was complete, reversible, and noncompetitive. 1-Octanol also antagonized ethanol inhibition of BMP-7 morphogenesis in NG108-15 cells. 1-Octanol and related compounds may prove useful in dissecting the role of altered cell adhesion in ethanol-induced injury of the nervous system.
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PMID:Antagonists of alcohol inhibition of cell adhesion. 1072 68

The p53-related p73 and p63 genes encode proteins that share considerable structural and functional homology with p53. Despite similarities, their deletion in mice has different outcomes, implying that the three genes may play distinct roles in vivo. Here we show that endogenous p73 levels increase in neuroblastoma cells induced to differentiate by retinoic acid and that exogenously expressed p73, but not p53, is sufficient to induce both morphological (neurite outgrowth) and biochemical (expression of neurofilaments and neural cell adhesion molecule (N-CAM); down-regulation of N-MYC and up-regulation of pRB) markers of neuronal differentiation. This activity is shared, to different extents, by all p73 isoforms, whereas the transcriptionally inactive mutants of p73 isoforms are ineffective. Conversely, blockage of endogenous p73 isoforms with a dominant negative p73 results in the abrogation of retinoid-induced N-CAM promoter-driven transcription. Our results indicate that the p73 isoforms activate a pathway that is not shared by p53 and that is required for neuroblastoma cell differentiation in vitro.
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PMID:Induction of neuronal differentiation by p73 in a neuroblastoma cell line. 1080 58

Polysialic acid (PSA) is a dynamically regulated carbohydrate modification of the neural cell adhesion molecule NCAM, which is implicated in neural differentiation and cellular plasticity. The cloning and characterization of two polysialyltransferases, termed ST8SiaII (STX) and ST8SiaIV (PST), opened up new perspectives in the search for factors that control this unique cell surface glycosylation. In vitro and transfection approaches revealed that ST8SiaII and ST8SiaIV are independently capable of synthesizing PSA on NCAM with slightly different specificities towards the major NCAM isoforms and glycosylation sites. Their overlapping but distinct expression patterns during brain development point towards an independent transcriptional regulation. However, the factors driving their joint or distinct expression, as well as the significance of divergent expression patterns in vivo, are not yet understood. In the present study, the mRNA expression of ST8SiaII and ST8SiaIV was comparatively analyzed in neuronal differentiation of PSA-positive human neuroblastoma cell lines induced by retinoic acid (RA), phorbolester, or growth factors. Using a semiquantitative RT-PCR strategy, we demonstrated a general decrease in the mRNA level of ST8SiaII upon differentiation of SH-SY5Y and LAN-5 cells. In contrast, a drastic increase of ST8SiaIV was specifically induced by RA-treatment of SH-SY5Y cells. To explore the significance of these changes, the cellular capacity to perform PSA synthesis and the degree of NCAM polysialylation were analyzed. Our data indicate that the increased expression of ST8SiaIV enables an accelerated polysialylation of NCAM, which, however, is not converted into higher amounts of PSA.
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PMID:Retinoic acid-induced changes in polysialyltransferase mRNA expression and NCAM polysialylation in human neuroblastoma cells. 1110 12

In order to determine how glycosylation changes associated with cellular differentiation may be influenced by the basal cellular sialylation potential, the effect of retinoic acid (RA)-induced differentiation was investigated in neuroblastoma cells expressing differing levels (and activities) of the alpha2,6(N) sialyltransferase (ST6N) enzyme. The increase in ST activity was proportional to the basal cellular sialylation potentials with the high activity clones showing the greatest increase. This was paralleled by an up-regulation of the level of overall sialoglycoprotein glycosylation level. An increase in the levels of the polysialic acid (PSA) epitope was associated with a parallel increase in the levels of the neural cell adhesion molecule (NCAM) protein backbone although there was no overall change in the PSA:NCAM ratio following RA treatment.
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PMID:Retinoic acid induction of sialyltransferase activity in neuroblastoma cells of differing sialylation potentials. 1144 79

Polysialic acid (PSA), which is abundantly expressed in the embryonic brain, plays important roles in neural development and plasticity. PSA is also expressed in tumors of neural crest origin such as neuroblastoma. However, the biologic significance of PSA in these tumors has not been elucidated. In this study, we examined the expression of PSA as well as 2 polysialyltransferases, PST and STX, in various tumor cell lines. PST and STX were simultaneously expressed in all the tumor cells positive for PSA. However, even in the tumor cells negative for PSA, they expressed PSA after transfection of neural cell adhesion molecule (NCAM) cDNA when these cells expressed PST, suggesting that the presence of NCAM was critical for PSA expression. To determine the role of PSA in tumor growth and development, we established tumor sublines expressing or lacking PSA from PC-14 or NCI-H146 cells. Although significant differences of growth rates between the PSA-positive and -negative tumor cells were not detected in vitro, the PSA-positive tumor cells hardly produced detectable tumors when injected into nude mice subcutaneously or intravenously. In addition, the PSA-positive tumor cells adhered less to a basement membrane matrix Matrigel than did the PSA-negative tumor cells. These results altogether suggested that PSA significantly reduced tumor formation in the transplanted xenografts through attenuation of cell-cell or cell-matrix interactions by its large, negatively charged glycans in this particular animal model system.
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PMID:Effect of polysialic acid on the tumor xenografts implanted into nude mice. 1166 97

Valproic acid (VPA) has been shown to induce growth-arrest and differentiation of human neuroectodermal tumors similarly to several other fatty acids. In the present study, we show that continuous VPA treatment together with Interferon-alpha (INF-alpha) synergistically inhibited cell growth of a well-established model of neuroblastoma (NB) differentiation using the human N-myc amplified cell line BE(2)-C. Suppression of tumor growth was accompanied by morphological features of neuronal differentiation and inhibition of histone deacetylase activity. Furthermore, induction of differentiation was concomitant with altered expression of genes related to malignant phenotype such as down-regulation of N-myc, induction of bcl-2 and neural cell adhesion molecule. Production of inhibitors of angiogenesis like thrombospondin-1 and activin A was up-regulated in differentiated NB cells. Treatment with VPA alone decreased the ability of BE(2)-C cells to adhere to and penetrate human endothelium. All these effects of VPA were significantly enhanced when combined with INF-alpha which on its own had little or no effect. These results suggest that combination of VPA and INF-alpha may provide a novel therapeutic strategy for NB due to enhanced inhibition of tumor cell growth, induction of tumor differentiation and suppression of malignant biology by reduced angiogenic and decreased metastatic potentials.
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PMID:Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: enhancement by combination with interferon-alpha. 1174 48

To identify molecular interaction partners of the cellular prion protein (PrP(C)), we sought to apply an in situ crosslinking method that maintains the microenvironment of PrP(C). Mild formaldehyde crosslinking of mouse neuroblastoma cells (N2a) that are susceptible to prion infection revealed the presence of PrP(C) in high molecular mass (HMM) protein complexes of 200 to 225 kDa. LC/MS/MS analysis identified three murine splice-variants of the neural cell adhesion molecule (N-CAM) in the complexes, which isolate with caveolae-like domains (CLDs). Enzymatic removal of N-linked sugar moieties did not disrupt the complexes, arguing that the interaction of PrP with N-CAM occurs through amino acid side-chains. Additionally, similar levels of PrP/N-CAM complexes were found in N2a and prion-infected N2a (ScN2a) cells. With the use of an N-CAM-specific peptide library, the PrP-binding site was determined to comprise beta-strands C and C' within the two consecutive fibronectin type III (FNIII) modules found in proximity of the membrane-attachment site of N-CAM. As revealed by in situ crosslinking of PrP deletion mutants, the PrP face of the binding site is formed by the N terminus, helix A (residues 144-154) and the adjacent loop region of PrP. N-CAM-deficient (N-CAM(-/-)) mice that were intracerebrally challenged with scrapie prions succumbed to disease with a mean incubation period of 122 (+/-4.1, SEM) days, arguing that N-CAM is not involved in PrP(Sc) replication. Our findings raise the possibility that N-CAM may join with PrP(C) in carrying out some as yet unidentified physiologic cellular function.
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PMID:Binding of neural cell adhesion molecules (N-CAMs) to the cellular prion protein. 1174 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

Polysialic acid (PSA) is a regulatory epitope of neural cell adhesion molecule (NCAM) in homophilic adhesion of neural cells mediated by NCAM, is also known to be re-expressed in several human tumors, thus serves as an oncodevelopmental antigen. In this study, using a recently developed ultrasensitive chemical method in addition to immunochemical methods, growth stage-dependent and retinoic acid (RA)-induced differentiation-dependent changes of PSA expression in human neuroblastoma (IMR-32) and rat pheochromocytoma (PC-12) cells were analyzed both qualitatively and quantitatively. Both IMR-32 and PC-12 cells expressed PSA on NCAM, and the level of PSA expressed per unit weight of cells increased with post-inoculation incubation time. The most prominent feature was seen at the full confluence stage. RA induced neuronal differentiation in both IMR-32 and CP-12 cells that paralleled the change in the PSA level. Chemical analysis revealed the presence of NCAM glycoforms differing in the degree of polymerization (DP) of oligo/polysialyl chains, whose DP was smaller than 40. DP distribution of PSA was different between the cell lines and was changed by the growth stage and the RA treatment. Thus DP analysis of PSA is important in understanding both mechanism and biological significance of its regulated expression.
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PMID:Dynamic change of neural cell adhesion molecule polysialylation on human neuroblastoma (IMR-32) and rat pheochromocytoma (PC-12) cells during growth and differentiation. 1202 85


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