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)

In this study we have determined the binding specificities of four different neuronal cell types to tenascin-C (TN-C) and laminin using a cell adhesion assay. TN-C was repulsive for small cerebellar neurons and PC12 phaeochromocytoma cells, since after short-term adhesion to the substrate-bound molecule with a maximum of cell binding at 45 min, the cells detached from the substrate and after 22 h only about 25% of the originally adherent cells were still bound. For N2A neuroblastoma cells and retinal cells TN-C was an adhesive substrate, since the number of adherent cells did not decrease after the initial attachment period. All four cell types adhered well to laminin at all time points studied. For short-term adhesion of small cerebellar neurons and PC12 cells two binding sites were identified on TN-C, one being localized within the epidermal growth factor-like repeats three to five and the second within fibronectin type III-like repeats three and four. One binding site for N2A and retinal cells was localized within fibronectin type III-like repeat seven. Binding of small cerebellar neurons to TN-C was dependent on Ca2+, but not on Mg2+ and was inhibitable by polyclonal antibodies to beta 1 integrin. Short-term adhesion of small cerebellar neurons was also inhibitable with a mixture of recombinant fragments of TN-C encompassing the whole molecule, although the specific inhibitory activity of this mixture was ten-fold lower on a molar basis when compared to the native molecule. Our observations indicate that different neuronal cell types use distinct binding sites on TN-C for repellent or adhesive interactions and that beta 1 integrin is involved in the recognition event leading to repulsion of small cerebellar neurons.
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PMID:Distinct sites on tenascin-C mediate repellent or adhesive interactions with different neuronal cell types. 882 Oct 32

IMR32, a neuroblastoma cell line, and CADO LC6, a small cell lung cancer (SCLC) cell line, extended neurite-like processes when cultured on fibronectin (FN)-coated surfaces or cultured in a serum-free medium. Monoclonal antibodies against the integrin beta 1 subunit inhibited this process formation, suggesting that their morphological change is initiated by beta 1 integrin-dependent signal transduction to the cell interior. Anti-phosphorylation level of a 100-kDa protein, but not 125-kDa focal adhesion kindase, correlated well with the morphological change in both cell lines. This 100-kDa protein phosphorylation did not accompany FN-induced morphological changes in NIH 3T3 fibroblasts or A549 adenocarcinoma cells. These findings suggest that neuroblastoma and SCLC may share beta 1 integrin-mediated signaling events distinct from nonneuronal cells.
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PMID:A 100-kDa protein tyrosine phosphorylation is concurrent with beta 1 integrin-mediated morphological differentiation in neuroblastoma and small cell lung cancer cells. 883 61

The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways.
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PMID:Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related. 884 7

The effects of transforming growth factor-beta1 (TGFbeta) on two human neuroblastoma cell lines, LAN-5 and SK-N-AS, and one human glioblastoma cell line, GL15, were evaluated. Of the three cultures, only two, SK-N-AS and GL15, had a complete response to TGFbeta, with induction of the following effects: (i) inhibition of cell proliferation; (ii) up-regulation of the extracellular matrix glycoprotein fibronectin, together with down-regulation of the VLA5 integrin receptor; (iii) up-regulation of histotype-specific cytoskeletal intermediate filaments (neurofilaments for neuroblastoma and GFAP for glioblastoma); and (iv) increase in the glycoprotein CD44, only in SK-N-AS. In the third cell line, neuroblastoma LAN-5, the effects exerted by TGFbeta consisted only of (i) neurofilament increase and (ii) morphological differentiation. The TGFbeta receptor pattern was different in each culture: SK-N-AS expressed low rates of type I and type II receptors and high rates of type III receptor; LAN-5 expressed high rates of type I, low rates of type II, and no type III; GL15 expressed high rates of all three receptors. These data suggest that TGFbeta can induce a histotype-specific cell maturation and that the neuroblastoma expressing low type II and at the same time lacking type III receptor responds only partially to TGFbeta, with induction of neural differentiation but without inhibition of cell growth.
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PMID:Transforming growth factor beta regulates differentiation and proliferation of human neuroblastoma. 894 Feb 58

In order to clarify the relationship between invasiveness and loss of cellular differentiation in tumor cells, we studied the invasive properties on Matrigel of (a) a series of clones we isolated from human neuroblastoma LaN1 and Platt cell lines inducible to differentiation by adhesion on fibronectin, and (b) SY5Y human neuroblastoma cells inducible to differentiation by retinoic acid. We found that, regardless of the parental line, the more differentiated clones were scarcely invasive, while the less differentiated clones showed a higher degree of invasiveness. Differences in invasiveness between differentiated and non-differentiated neuroblastoma clones did not reflect differences in adhesiveness to laminin, the major component of Matrigel. The retinoic acid-sensitive SY5Y human neuroblastoma cells also reduced their invasiveness on Matrigel after differentiation induced by growth in media supplemented with retinoic acid. These results point to an inverse relationship between differentiative properties and invasiveness in human neuroblastoma cell lines.
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PMID:Inverse relationship between invasiveness and differentiative capacity in different human neuroblastoma cell lines. 905 55

Neuroblastoma (NB) is the most common solid malignant tumor found in pediatric patients and the liver is one of the major sites of metastasis. To investigate the organ specificity of metastatic distribution, the adherence behavior of tumor cells was studied. The data presented are based on studies using a metastatic murine cell line C1300. In vivo, not only intrasplenic but also intravascular injection of C1300 NB cells consistently results in hepatic metastasis formation in syngeneic A/J mice. An in vitro assay was used in which C1300 NB cell attachment to cryostat sections of liver, spleen, brain, kidney and lung obtained from normal A/J mice was measured to compare organ-specific adhesion. A good correlation was found between their metastatic potential in the liver and the adhesion to the liver sections; C1300 NB cells adhered preferentially to liver cryostat sections. Enzyme assays indicated that cell surface glycoproteins were involved in cell adhesion. An adhesion assay with extracellular matrix proteins demonstrated that C1300 NB cells adhered preferentially to vitronectin and fibronectin, and the adherence was strongly inhibited by Arg-Gly-Asp (RGD)-containing peptides. Furthermore, adhesion of C1300 NB cells to liver cryostat sections could be blocked by the synthetic peptide GRGDS. This indicates that the interaction between RGD-containing matrix adhesion protein and cells has an important role for the specific adhesion of C1300 NB cells. The results suggested that tumor cell adhesion to liver cryostat sections could provide a useful tool in the study of host-tumor interactions in the metastasis of NB.
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PMID:Organ-specific adhesion of neuroblastoma cells in vitro: correlation with their hepatic metastasis potential. 912 51

We have examined the effects of oleoylanilide, one of the main candidates in the etiology of the toxic oil syndrome, in the neuroblastoma cell line N2A. Oleoylanilide treatment causes two kinds of phenomena: alteration of the actin cytoskeleton, creating a brush-like protrusion of actin at the periphery of the cells, and reduction of the adhesiveness of these cells to laminin and fibronectin, two of the main components of the extracellular matrix in the central nervous system. These effects could be correlated with symptoms shown in the acute and chronic phases of the disease.
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PMID:Oleoylanilide, a possible causative agent of toxic oil syndrome, interferes with the cytoskeleton in a neuronal cell line. 913 31

Human SH-SY5Y neuroblastoma cells were induced to neuronal differentiation by using 12-0-tetradecanoylphorbol-13-acetate (TPA) and retinoic acid (RA). Both treatments rapidly induced long neurites and increased the content of neurofilaments as shown by immunocytochemistry and immunoblotting. Immunoprecipitation and immunoblotting of the culture medium with monoclonal antibodies demonstrated a rapid onset of synthesis and secretion of Mr 280,000 tenascin (Tn) polypeptide with TPA and both Mr 280,000 and 190,000 Tn polypeptides with RA and an increased secretion of extradomain A cellular fibronectin (EDA-Fn) upon both treatments. Upon RA treatment both Tn polypeptides were also found in extracellular matrix preparations of the differentiated cells. A diffuse extracellular Tn immunoreactivity and a distinct cytoplasmic reaction were seen in differentiated cells especially after exposure to monensin to inhibit cellular secretion. Instead, immunoprecipitation experiments suggested that laminin was synthesized by the cells but was not upregulated upon differentiation. Experiments with purified Tn, used to coat the culture substratum, demonstrated that the undifferentiated cells were unable to adhere or spread on Tn but rapidly acquired the spreading capacity upon differentiation with the inducing agents. In immunofluorescence and immunoblotting the undifferentiated cells presented only a faint heterogenous reaction for beta1 integrin (Int) subunit, whereas cells exposed to RA presented a strong reaction for the Int alpha1 and beta1 subunits, hence suggestive of Int alpha1beta1, and for Int alpha(v) subunit. Cells exposed to TPA showed an enhanced immunoreaction for Int alpha2 and beta1 subunits, suggestive of Int alpha2beta1, and for Int alpha(v) subunit. Immunoreactivity for Int alpha(v) located to distinct punctate plaques in the differentiated cells after both inducing agents. The results suggest that Tn is produced by cultured neuronally differentiating cells, and it is accompanied by the acquitance of an adhesion receptor for Tn.
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PMID:Neuronal differentiation in SH-SY5Y human neuroblastoma cells induces synthesis and secretion of tenascin and upregulation of alpha(v) integrin receptors. 921 89

Pentoxifylline (PTX) has been reported to have both direct and indirect anti-tumor effects in experimental tumor models. We studied the effect of PTX on (1) the proliferation of Neuro2a mouse neuroblastoma cells in vitro and in vivo, (2) spontaneous and experimental metastasis, (3) tumor cell membrane fluidity and (4) adhesion to a fibronectin-coated surface. PTX significantly reduced the proliferation of Neuro2a cells in vitro as determined by DNA measurement (P < 0.01) and total cell count (P < 0.02). In vivo, PTX reduced the growth of subcutaneously transplanted primary tumors in syngeneic A/J mice (P < 0.01; n = 15). All seven animals (100%) receiving intravenous tumor cells developed extensive liver metastasis. In contrast, only 1/11 (9%) of animals pre-treated with oral PTX and injected with PTX-treated cells developed liver metastases. Of five mice receiving PTX-treated cells without oral pretreatment of PTX, two out of five (40%) developed liver metastases. There was a slight, but not significant (P = 0.08) increase in both experimental and spontaneous lung metastases formation in PTX-treated animals. However, tumor nodule formation on the lung surface was inefficient. PTX also increased membrane fluidity of the Neuro2a cells and significantly decreased tumor cell adhesion to fibronectin-coated microtiter wells (P < 0.01). We conclude that PTX has a cytostatic effect on the Neuro2a mouse neuroblastoma and exerts an anti-tumor effect on liver metastases following intravenous administration of neuroblastoma cells. Whether these results are directly related to the changes in membrane properties caused by pentoxifylline remains to be established.
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PMID:The effect of pentoxifylline on spontaneous and experimental metastasis of the mouse Neuro2a neuroblastoma. 921 35

Six human neuroblastoma (NB) cell lines of different type: three neuronal, one mixed and two epithelial, were studied for their responsiveness to interferon gamma (IFNgamma). The effects of IFNgamma on cell growth rate and morphology were first evaluated: the replication was significantly inhibited in five out of six NB, while a neural morphological maturation was evident only in the three neural NB. Whether IFNgamma could also control the synthesis of two extracellular matrix glycoproteins, often involved in NB differentiation, laminin (LM) and fibronectin (FN), was then analyzed. Both glycoproteins increased after IFNgamma treatment in all neural and in the mixed NB, while they slightly decreased in one and did not change significantly in the other epithelial NB. Therefore, IFNgamma determines the up-regulation of FN and LM, while inducing NB cell growth inhibition and neural differentiation. These data support the hypothesis that the expression of the two extracellular matrix glycoproteins is controlled by IFNgamma during the complex event of NB terminal maturation.
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PMID:Interferon gamma modifies fibronectin and laminin synthesis in human neuroblastoma cell lines. 949 52


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