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

The neural cell adhesion molecules L1 and N-CAM have been suggested to interact functionally by formation of a complex between the two molecules (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990. J. Cell Biol. 110:193-208). To determine the molecular mechanisms underlying this functional cooperation, we have studied the contribution of carbohydrates to the association of the two molecules at the cell surface. Aggregation or adhesion between L1- and N-CAM-positive neuroblastoma N2A cells was reduced when the synthesis of complex and/or hybrid glycans was modified by castanospermine. Fab fragments of polyclonal antibodies to L1 inhibited aggregation and adhesion of castanospermine-treated cells almost completely, whereas untreated cells were inhibited by approximately 50%. Fab fragments of polyclonal antibodies to N-CAM did not interfere with the interaction between castanospermine-treated cells, whereas they inhibited aggregation or adhesion of untreated cells by approximately 50%. These findings indicate that cell interactions depending both on L1 and N-CAM ("assisted homophilic" binding) can be reduced to an L1-dominated interaction ("homophilic binding"). Treatment of cells with the carbohydrate synthesis inhibitor swainsonine did not modify cell aggregation in the absence or presence of antibodies compared with untreated cells, indicating that castanospermine-sensitive, but swainsonine-insensitive glycans are involved. To investigate whether the appropriate carbohydrate composition is required for an association of L1 and N-CAM in the surface membrane (cis-interaction) or between L1 on one side and L1 and N-CAM on the other side of interacting partner cells (trans-interaction), an L1-positive lymphoid tumor cell line was coaggregated with and adhered to neuroblastoma cells in the various combinations of castanospermine-treated and untreated cells. The results show that it is the cis-interaction between L1 and N-CAM that depends on the appropriate carbohydrate structures.
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PMID:Functional cooperation between the neural adhesion molecules L1 and N-CAM is carbohydrate dependent. 229 83

The neural cell adhesion molecule L1 can be induced by antibodies in indirect immunofluorescence procedures to co-redistribute on the surface membrane of cultured mouse neuroblastoma cells with the 180 kDa component of N-CAM, but not with the 140 kDa component of N-CAM, the H-2 histocompatibility antigen or antigens recognized by polyspecific antibodies to mouse liver membranes. These observations indicate a differential and close molecular association between L1 and the N-CAM component with the larger intracellular domain.
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PMID:Molecular association of two neural cell adhesion molecules within the surface membrane of cultured mouse neuroblastoma cells. 352 11

The cell-adhesion molecules N-CAM (neural cell-adhesion molecule) are ligands in the formation of cell-cell bonds and have been shown to play important roles during neuro-ontogenesis. They exist in several molecular forms which differ at the protein and carbohydrate levels. The regulation of the expression of these different forms is an important issue that bears on such questions as to how adhesive interactions between cells are modulated during morphogenesis. In the present study we have used N-CAM cDNA clones to investigate the expression of the cognate mRNAs in the mouse and rat brain and in 2 neural cell lines. The results were compared with the levels of the different N-CAM proteins. We made the following observations. A complex set of 5 size classes of mRNAs--which show developmental, regional, and cell-type-dependent variations in their expression--hybridize to 1 of our cDNA probes. While embryonic brain contains N-CAM gene transcripts 7.4, 6.7, and 4.3 kilobases (kb) in length, 2 additional mRNAs of 5.2 and 2.9 kb appear postnatally. Transformed brain cells of an astrocytic character express predominantly mRNAs of 6.7, 4.3, and 2.9 kb and a neuroblastoma line those of 7.4, 6.7, 4.3, and 2.9 kb. There are important quantitative changes in the amount of N-CAM message expressed during brain development, with a peak around birth, suggesting that N-CAM synthesis is controlled at the transcriptional level. A comparison of N-CAM protein and mRNA levels reveals a striking correlation between the relative concentrations of the Mr 120,000 N-CAM protein (N-CAM120) and the 5.2 kb transcript.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential expression of mouse neural cell-adhesion molecule (N-CAM) mRNA species during brain development and in neural cell lines. 373 70

Two cell surface molecules found in mouse brain, N-CAM and the L1 antigen, were compared in terms of their cell adhesion function, polypeptide structures, antigenic determinants and distribution in cerebellar tissue. Fab fragments of polyclonal antibodies to either N-CAM or L1 antigen only partially inhibited the rate of calcium-independent aggregation of neuroblastoma N2A cells, whereas complete and more efficient inhibition was obtained when they were used in combination. Despite the functional similarity, comparison of the electrophoretic behaviour of the purified molecules and of their proteolytic fragments shows that the L1 antigen polypeptide is distinct from that of N-CAM. In addition, no antigenic cross-reactivity was detected between the two molecules. In cryostat sections of cerebellum from young post-natal mice, N-CAM was found to be present in all cell and neurite layers, whereas L1 antigen was expressed only in regions containing post-mitotic cells. These results indicate that two chemically and histochemically distinct cell surface polypeptides can contribute to the calcium-independent adhesiveness of neural cells, and suggest that their differential expression might cause adhesive specificity among cells of developing neural tissues.
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PMID:Comparison of two cell surface molecules involved in neural cell adhesion. 620 60

Cell surface molecules have been implicated in cell interactions which underlie formation of the nervous system. The analysis of the functional properties of such molecules has profited from the combined use of antibodies and cell culture systems. It has been suggested that the interplay between these molecules modulates cell-to-cell interaction at critical developmental stages. In the mouse, N-CAM and L1 antigen have been shown to mediate Ca2+-independent adhesion among neural cells. N-CAM plays a role in fasciculation of neurites and formation of neuromuscular junction. L1 is apparently not involved in synaptogenesis, but in migration of granule cell neurones in the developing mouse cerebellar cortex. The two antigens are distinct molecular and functional entities which act synergistically in aggregation of neuroblastoma and early postnatal cerebellar cells. In view of a certain similarity in function between the two groups of molecules, it was not surprising to find that structural similarities are detectable by the monoclonal antibody L2. We show here that a carbohydrate moiety recognized by L2 and HNK-1 monoclonal antibodies, is present in mouse N-CAM and L1. The L2 epitope appears on all major neural cell types but not all N-CAM molecules express it. This heterogeneity points to a previously undetected molecular diversity which may have functional implications for modulating cell adhesion during development.
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PMID:Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1. 620

L1 is a transmembranal homophilic cell adhesion molecule of the immunoglobulin superfamily expressed by neural and lymphoid cells. The heat-stable antigen (HSA, murine CD24) nectadrin is a highly and heterogeneously glycosylated glycophosphatidylinositol-linked differentiation antigen of haematopoietic and neural cells. L1 and nectadrin have been shown to mediate cell adhesion and intracellular Ca2+ signals in neurons and B lymphoblasts, respectively. Here we show that nectadrin is co-expressed with L1 in murine cerebellar granule cell neurons and neuroblastoma N2A cells. Purified nectadrin bound to L1 with an apparent binding ratio of five nectadrin molecules to one L1 molecule at saturation. Binding between nectadrin and purified N-CAM was not observed. In co-capping experiments nectadrin co-redistributed with L1 and N-CAM. Since in these cells N-CAM and L1 cohere by cis-binding nectadrin appears to join the L1-N-CAM complex through binding to L1. Antibodies to each L1 and nectadrin evoked small increases in the intracellular Ca2+ concentration. However, when both antibodies were added together or in tandem to the cells, a strong intracellular Ca2+ signal was measured that was at least 6- and 10-fold stronger than the signal separately induced by L1 and nectadrin antibodies respectively. Such a cooperative effect was not observed in B lymphoblasts, using the same antibodies, or in neurons, using a combination of L1 and Thy-1 antibodies. Both the weak Ca2+ signal mediated by L1 alone and the enhanced signal jointly triggered by antibodies to L1 and nectadrin were inhibited by phorbol 12-myristate 13-acetate and were not significantly affected by Ni2+ and Cd2+ cations, suggesting that they are related to one another and involve recruitment of intracellular Ca2+. Nectadrin therefore appears to join a functional complex of neuronal adhesion molecules and to potentiate the signal transduction pathway of L1, possibly in response to neuron-neuron contact formation.
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PMID:Evidence for cis interaction and cooperative signalling by the heat-stable antigen nectadrin (murine CD24) and the cell adhesion molecule L1 in neurons. 761 34

The reactivity of a mAb (M16) raised against a small cell lung carcinoma line is described. M16 identifies a surface antigen expressed on cells of neuroectodermal origin following activation, as well as neoplastic transformation. M16 antigen expression is increased on retinoblastoma and neuroblastoma cell lines upon 'in vitro' stimulation and it is induced 'in vivo' on glial cells activated following brain injury. Furthermore, glial tumors show levels of M16 molecule expression increasing with the degree of malignancy, and in a retinoblastoma cell line, the expression of M16 was inversely related to the level of HLA-Class I and N-CAM antigens. The M16 antigen may represent a marker of both activation and neoplastic progression for neuroectodermal cells.
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PMID:Biochemical characterization and membrane expression of an antigen shared by activated and neoplastic cells of neuroectodermal origin. 770 33

To identify cell adhesion molecules (CAMs) expressed by mammalian motoneurons, we applied the polymerase chain reaction to a murine motor neuron-like cell line, NSC-34. Using primers derived from a group of L1-related CAMs, we cloned two alternatively spliced forms of mouse L1, which differ by a 12-base-pair insert, plus putative murine orthologs of the chicken cell adhesion molecules Nr-CAM/Bravo and neurofascin. All four mRNAs are expressed in NSC-34 cells, but only neurofascin and the insert-minus form of L1 are expressed in its neuroblastoma parent, N18TG2. Analysis of RNA in neonatal tissues reveals expression largely restricted to the brain and spinal cord. In situ hybridization histochemistry of spinal cord shows that motoneurons express L1, Nr-CAM, and neurofascin as well as N-CAM. L1 and N-CAM RNAs are detected throughout the period studied (from embryonic day [E]11 to postnatal day [P]28), whereas Nr-CAM is expressed only at early ages (< E15) and neurofascin is predominantly expressed postnatally. Moreover, each CAM is expressed by distinct subsets of neighboring cells and at distinct times. For example, Nr-CAM mRNA is present in floor plate cells of embryonic spinal cord, whereas neurofascin is expressed by a subset of glia postnatally. Finally, we show that each CAM has a distinct spatiotemporal pattern of expression in dorsal root ganglia.
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PMID:Expression of four immunoglobulin superfamily adhesion molecules (L1, Nr-CAM/Bravo, neurofascin/ABGP, and N-CAM) in the developing mouse spinal cord. 770 55

Gestational exposure to ethanol causes defects in neuronal migration, fasciculation, and synaptogenesis, developmental events that depend on the patterned expression and function of cell adhesion molecules (CAMs). Recombinant human osteogenic protein-1 (hOP-1) increases cell-cell adhesion and promotes cell clustering in proliferating neuroblastoma x glioma hybrid NG108-15 cells by strongly inducing N-CAM and L1. Here we show that concentrations of ethanol achieved during social drinking inhibit hOP-1-induced cell clustering without affecting cell proliferation, the induction and cell surface expression of N-CAM and L1, or the alternative splicing and sialylation of N-CAM. This inhibition was reproduced by other alcohols in proportion to their chain length, but not by teratogenic anticonvulsants or phenylalanine. Ethanol inhibition of hOP-1 morphogenesis was inversely proportional to the concentration of hOP-1 and, hence, to the levels of N-CAM and L1. Low concentrations of ethanol (IC50 5-10 mM) inhibited cell-cell adhesion in hOP-1-treated cells, and this action too was reproduced more potently by propanol and butanol. Ethanol may perturb brain and skeletal development by inhibiting CAM-mediated cell-cell interactions.
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PMID:Ethanol inhibits neural cell-cell adhesion. 813 68

We have established a new human neuroblastoma (NB) cell line from the bone marrow of a 1-year-old boy with NB, termed JK-NB1, which showed constant growth for as long as 17 months or more, similar phenotype to those of other reported NB cell lines, colony formation in liquid and methylcellulose culture, N-myc amplification, high expression of N-CAM, and NSE production. We have tried to induce LAK cell activity with peripheral blood mononuclear cells (PBMCs) from the patient against the autochthonous JK-NB cells. PBMCs from the patient proliferated up to 20-fold in the presence of interleukin-2 (IL-2) after 9 days of incubation, and LAK activity increased up to 24.7-fold and killed all of the JK-NB1 cells. In contrast, IL-2 alone or PBMCs from the patient or a healthy adult donor had little effect on the growth of NB cells. These data suggest that it is possible to induce LAK cell activity in PBMCs from the patient against autologous as well as allogenic NB cells, and provide a rational base for the clinical use of IL-2 as one of the treatments for NB.
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PMID:Establishment of a neuroblastoma cell line and induction of lymphokine-activated killer (LAK) activity against the autologous neuroblastoma cell line. 814 11


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