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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interactions between neural cell surfaces seem to be of prime importance during neuroontogenesis, and responsible for the guidance of migrating neuroblasts and growing axons and for the formation of synapses. Little is known about the underlying molecular mechanisms, but most hypotheses imply the existence of cell-surface molecules that mediate the formation of transient or permanent bonds between neural cells. Recently, a membrane glycoprotein called neural cell adhesion molecule (N-CAM) has been characterized in chick and rodent nervous tissue that appears to act as a ligand in adhesion among neural cell bodies or neurites. We have identified a mouse neural surface glycoprotein, named BSP-2 (ref. 7), which by criteriaof electrophoretic migration, developmental changes, amino acid and sugar composition seems to be closely related or identical to N-CAM. Both BSP-2 (refs 8, 9) and N-CAM undergo conversion from an embryonic to an adult form during brain development and it has been suggested that this transition changes the adhesive properties or the binding specificity of the molecule. Using a neuroblastoma line to study functional differences between embryonic and adult BSP-2/N-CAM molecules, we show here that liposomes bearing adult BSP-2 but not those bearing the embryonic form adhere to neuroblastoma cells, demonstrating that the two forms do indeed possess different binding properties.
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PMID:Adult and embryonic mouse neural cell adhesion molecules have different binding properties. 687 55

Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low-frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect.
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PMID:Regulated expression of the neural cell adhesion molecule L1 by specific patterns of neural impulses. 748 27

The MSD1 region of neural cell adhesion molecule (NCAM) was originally described as being spliced into the 120-kDa isoform of NCAM isolated from muscle. The 105 bp region is inserted between exons 12 and 13 and actually consists of three separate exons, MSD1a, MSD1b and MSD1c of 15, 48, 42 bp, respectively. In addition, a further exons consisting of a single triplet has been designated MSD1d, making the full insert size 108 bp. As the MSD1 region was originally described as being selectively expressed in muscle tissue, we have investigated whether it is also present on tumours of rhabdoid origins and whether its presence can be used as the diagnostic marker to distinguish other small round cell tumours of childhood, such as neuroblastoma. Using a variety of human tumour cell lines, we demonstrated the presence of the MSD1 region on all rhabdomyosarcomas investigated. However, neuroblastoma cell lines only expressed subcompartments of the MSD1 region. The MSD1c exon was not spliced into the NCAM molecules isolated from any of the neuroblastoma cell lines investigated. On the basis of this finding, it appears that neuroblastoma and rhabdomyosarcoma can be distinguished by the expression of MSD1c mini-exon. Further studies are underway to attempt to define a monoclonal antibody that recognises the region, using mice immunised with synthetic peptides, and to confirm the finding using fresh biopsy material.
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PMID:Tissue-specific expression of neural cell adhesion molecule (NCAM) may allow differential diagnosis of neuroblastoma from embryonal rhabdomyosarcoma. 783 18

In this report, we show that the overexpression of tissue transglutaminase (tTG) in the human neuroblastoma cell line SK-N-BE(2) renders these neural crest-derived cells highly susceptible to death by apoptosis. Cells transfected with a full-length tTG cDNA, under the control of a constitutive promoter, show a drastic reduction in proliferative capacity paralleled by a large increase in cell death rate. The dying tTG-transfected cells exhibit both cytoplasmic and nuclear changes characteristic of cells undergoing apoptosis. The tTG-transfected cells express high Bcl-2 protein levels as well as phenotypic neural cell adhesion molecule markers (NCAM and neurofilaments) of cells differentiating along the neuronal pathway. In keeping with these findings, transfection of neuroblastoma cells with an expression vector containing segments of the human tTG cDNA in antisense orientation resulted in a pronounced decrease of both spontaneous and retinoic acid (RA)-induced apoptosis. We also present evidence that (i) the apoptotic program of these neuroectodermal cells is strictly regulated by RA and (ii) cell death by apoptosis in the human neuroblastoma SK-N-BE(2) cells preferentially occurs in the substrate-adherent phenotype. For the first time, we report here a direct effect of tTG in the phenotypic maturation toward apoptosis. These results indicate that the tTG-dependent irreversible cross-linking of intracellular protein represents an important biochemical event in the induction of the structural changes featuring cells dying by apoptosis.
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PMID:Tissue transglutaminase and apoptosis: sense and antisense transfection studies with human neuroblastoma cells. 793 79

The expression of neural cell surface glycoconjugates during development reflects the precise control of cellular adhesivity that is required for the exact positioning of the developing cells. We have investigated the effect of cell confluency state on the expression of key cell surface glycoconjugates using the mouse neuroblastoma cell line, neuro-2A. There was an up-regulation of expression of the neural cell adhesion molecule (NCAM) coincident with an increase in cell confluency state and a parallel decrease in the expression of the amyloid precursor protein, beta APP. The expression pattern of cell surface glycoconjugates in neuro-2A cells is therefore similar to that observed during the early embryonic period of development during which cells aggregate to form collectives.
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PMID:The effect of cell confluency state on the expression of neural cell surface glycoconjugates. 806 6

The neural cell adhesion molecule (N-CAM), is expressed in definite spatiotemporal patterns during development. To identify factors that may influence place-dependent n-cam gene expression, we have studied the binding and activation of the n-cam promoter by Pax-8, a member of the Pax family of transcription factors. Pax-8 increased n-cam promoter activity 13.4-fold in cellular co-transfection experiments, and a short segment of the promoter (-143 to -15) mediated the response. This region of the n-cam promoter produced a DNA-protein complex when incubated with either extracts from COS-7 cells transfected with the Pax-8 expression vector or a Pax-8/GST fusion protein. Pax-8 bound to the n-cam promoter through two TGCTCC motifs (designated PBS-1 and PBS-2) that resemble paired domain binding sites. Mutation of PBS-1 and PBS-2 eliminated Pax-8 activation of the n-cam promoter. Transfection of N2A neuroblastoma cells with the Pax-8 expression vector resulted in a 5-fold increase in the transcription of the endogenous n-cam gene. The combined results suggest that Pax-8 activates transcription of the n-cam gene through binding of sequences resembling paired domain binding sites in the n-cam promoter. The data raise the possibility that the n-cam promoter may be regulated by other members of the Pax gene family.
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PMID:Binding and activation of the promoter for the neural cell adhesion molecule by Pax-8. 807 51

The neural cell adhesion molecule (N-CAM), a member of the immunoglobulin gene super-family mediating homophilic cell-cell adhesion in a neuroendocrine system, is preferentially expressed in human small cell lung cancer (SCLC). Immunoprecipitation of a panel of SCLC cell lines by monoclonal antibodies (mAbs) specific for N-CAM detects mainly the 145-kDa isoform. This result was correlated with Northern blotting where a single 6.2-kb mRNA was detected in nine SCLC cell lines. To determine cDNA sequence encoding the N-CAM isoform, we selected several cDNA clones encoding N-CAM isolated from OS2-R, a SCLC cell line established in our laboratory. Based on the analysis of the full-length cDNA obtained from two clones, the sequence of this 145-kDa isoform was shown to be essentially identical to that of the 140-kDa N-CAM isoform of neuroblastoma except for a single base pair changed at position 1620 without changing amino acid encoded.
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PMID:Complementary DNA sequence encoding the major neural cell adhesion molecule isoform in a human small cell lung cancer cell line. 807 73

The neural cell adhesion molecule (NCAM) is thought to have an important role in cell-cell interactions during development. To better understand NCAM function, we studied the adhesion of mouse N2A neuroblastoma cells and Chinese hamster ovary cells to different forms of NCAM using a quantitative centrifugal cell adhesion assay that measures the rate of cell removal from experimental substrates. Embryonic brain NCAM is highly polysialylated and contains both 180- and 140-kDa polypeptide isoforms, whereas embryonic retinal NCAM is less highly polysialylated and contains primarily the 140-kDa isoform. For both forms, cell adhesion to substrate-immobilized NCAM was temperature dependent, cation independent, and time dependent. Cell adhesion to NCAM substrates was not directly affected by drugs inhibiting cytoskeletal function or cellular metabolism, suggesting that NCAM function does not depend critically on cytoskeletal function or metabolic activity. Cell adhesion to retinal NCAM was blocked by anti-NCAM antibodies, and adhesion was increased by neuraminidase treatment of both types of NCAM. Adhesion to brain NCAM was effectively blocked by anti-NCAM antibodies only after neuraminidase treatment, suggesting that these cells adhere to highly sialylated and less-sialylated NCAM by different mechanisms. We propose that multiple mechanisms of cell adhesion involving NCAM may exist in different tissues during development and that the state of polysialylation of NCAM is important in regulating the relative importance of these mechanisms.
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PMID:Multiple mechanisms of N2A and CHO cell adhesion to NCAM purified from chick embryonic brain and retina. 808 14

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

Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily that is expressed in the nervous system. We recently showed that human recombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregation of dividing neuroblastoma x glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neural cell adhesion molecule (N-CAM) (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10326-10330). Here we show that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s. OP-1 induction of L1 and N-CAM was unassociated with changes in cell proliferation and was not reproduced by cellular differentiation. The increased adhesiveness of hOP-1-treated NG108-15 cells could be inhibited in part by Fab fragments of an anti-L1 polyclonal antiserum. L1 and N-CAM expression first increased 12-18 h after hOP-1 treatment, reached a maximum after 2-3 days, persisted for up to 5 days, and returned to control levels 3 days after hOP-1 withdrawal. The increases in L1 and N-CAM protein levels were preceded or accompanied by large increases in the abundance of L1 and all detectable N-CAM mRNAs. Actinomycin D prevented the induction by hOP-1 of L1 and N-CAM mRNAs, suggesting that hOP-1 regulates immunoglobulin CAM gene transcription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.
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PMID:Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells. 822 84


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