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

Two cell clones [BE(2)-C and BE(2)-M17] derived from the human neuroblastoma cell line SK-N-BE(2) express corticotrophin-releasing hormone as well as interleukin-6 mRNA. Both genes are overexpressed, although with a different time course, following exposure to 5 microM retinoic acid, in parallel to the induction of neuroblastic differentiation. On the contrary, we are unable to detect interleukin-1 beta mRNA in these cell lines. Both cytokines are known to increase hypothalamic CRH mRNA. The production of cytokines and neuropeptides by neuroblastoma cells indicate a complex dialogue between tumour cells and anti-tumour immunity.
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PMID:Interleukin-6 and corticotrophin-releasing hormone mRNA are modulated during differentiation of human neuroblastoma cells. 140 16

The N-myc oncogene has been implicated in the pathogenesis of a number of human tumors, including childhood neuroblastoma and adult small cell lung cancer. We have isolated and characterized complementary DNA clones derived from a transcription unit, N-cym, located on the opposite DNA strand to N-myc, with extensive overlap existing between the 5' ends of the two transcription units. The N-cym gene, which can encode a 109-amino acid protein, is expressed during fetal development, as well as in tumor cell lines containing amplified N-myc loci, where it is expressed at very high levels. Although other examples of overlapping, opposite-strand eukaryotic genes exist, N-myc and N-cym are unique in that they appear to be coregulated in tumor cell lines under basal growth conditions and in response to the differentiating agent retinoic acid. This coregulation suggests that their protein products may be functionally interrelated during normal development and oncogenesis.
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PMID:Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc. 141 2

In order to obtain further insights into the expression of the known markers of secretory neuroendocrine dense core organelles, secretogranin II (SgII), chromogranin A (CgA), and chromogranin B (CgB) during neuronal differentiation, the immunolocalization of these proteins was studied by means of double immunofluorescence in both undifferentiated and retinoic acid-differentiated SH-SY5Y human neuroblastoma cells. The majority of undifferentiated cells was not immunolabeled for all three proteins. In the majority of differentiated cells, a clearly punctate SgII immunolabeling indicative of the presence of secretory organelles was present in the Golgi region, at the cell periphery, along the neurites and in growth cones. Only relatively few of the SgII-immunolabeled cells were also immunolabeled for CgA and CgB, and in a single cell the three proteins were not always present in the same organelles. These results, obtained in a cultured cell line, confirm the not necessarily parallel distribution of SgII, CgA, and CgB observed in different neuroendocrine tissues and suggest that SgII may be the best marker of human neuroblastoma cell differentiation.
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PMID:Immunolocalization of secretogranin II, chromogranin A, and chromogranin B in differentiating human neuroblastoma cells. 142 74

Neuroblastoma, a malignant neoplasm that arises in the adrenal medulla or sympathetic ganglion, is one of the most common solid tumors of childhood. Reports that neuroblastomas spontaneously mature to form benign ganglioneuromas have prompted investigations into the efficacy of using agents that induce neuronal differentiation in the treatment of this malignancy. Retinoic acid is one agent in particular that has been shown to induce growth inhibition and terminal differentiation of neuroblastoma cell lines in vitro. Using the human neuroblastoma cell line SMH-KCNR, we have investigated the role of the extracellular matrix protein thrombospondin in retinoic acid induced neuroblastoma differentiation. Treatment with retinoic acid results in a rapid induction (within 4 h) of thrombospondin (TSP) message which is independent of intervening protein synthesis and superinducible in the presence of cycloheximide. This suggests that TSP functions as a retinoic acid inducible immediate early response gene. A concomitant increase in both cell associated and soluble forms of TSP protein can be detected within 24 h of retinoic acid treatment. A functional role for TSP in SMH-KCNR differentiation was established in experiments which showed that exposure to anti-TSP monoclonal antibodies delay retinoic acid differentiation for 48 h. At the time the cells overcome the effects of TSP inhibition, laminin production becomes maximal. Treatment of the cells with a combination of anti-TSP and antilaminin antibodies results in complete inhibition of differentiation.
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PMID:Induction of thrombospondin 1 by retinoic acid is important during differentiation of neuroblastoma cells. 143 Feb 9

Cellular differentiation is often associated with striking changes in ganglioside metabolism. Because retinoic acid causes cellular differentiation in vitro, we have characterized its effect on ganglioside synthesis and shedding by LAN-5 human neuroblastoma cells. Three major observations were made: (a) 20 microM retinoic acid caused a marked (twofold) increase in cellular ganglioside content, with a slight relative enhancement in GD1a and GT1b synthesis, (b) ganglioside shedding increased in parallel with increased cellular ganglioside content, and also, unexpectedly, (c) retinoic acid caused a quantitatively similar increase in content of cell membrane phospholipids, which are also shed. We conclude that enhanced ganglioside synthesis and shedding by retinoic acid are part of a previously undescribed generalized stimulatory effect on membrane lipid metabolism.
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PMID:Alteration of neuroblastoma ganglioside metabolism by retinoic acid. 143 8

A cell line, established from a neuroblastoma patient, expresses NCAM and L1 cell adhesion molecules. Two chromosomal abnormalities were present in bone marrow (10%) and cell line (82%) metaphases: (i) a homogeneously staining region (HSR) at the distal part of chromosome 14, and (ii) an insertion of unidentified dark G-banding material in 1 p36. The identification in the patient of chr 14-HSR-positive tumour cells, before the in vitro adaptation, suggests a direct HSR formation without preceding double minutes (dms; or a very early in vivo dms----HSR transformation). N-myc was amplified in the HSR. Cells expressed proopiomelanocortin and corticotropin releasing factor mRNAs. Untreated cells were relatively differentiated; nevertheless they dramatically responded to retinoic acid, forming extensive neurites, growth-cones, cell-cell and cell-neurite junctions. Neurofilaments and synaptic figures containing many dense core granules were identified. This differentiation was irreversible. This cell line is therefore useful for the study of differentiation and in particular for the involvement of neurohormones in the differentiation process.
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PMID:An inducible cell line (Natasha), from a neuroblastoma patient with circulating HSR-positive blasts, expressing neurohormones. 150 9

The src-related intracellular protein tyrosine kinase Lyn is a signal transducing molecule for surface immunoglobulin M and is expressed predominantly in hemopoietic cells. We report here the expression of the lyn gene in human neuroblastoma. In surgical tumour samples lyn transcripts were found preferentially at early stages whereas they were barely detectable in highly malignant tumours. In a cloned human neuroblastoma cell line, Be(2)C, lyn mRNA levels increased during neuronal differentiation induced by retinoic acid. Lyn mRNA levels were undetectable and did not respond to retinoic acid in a glial-type neuroblastoma clone, SH-EP. Retinoic acid-induced glial differentiation was associated with a reduction of lyn transcripts in a clonal I-type neuroblastoma cell line, SH-IN, which shares properties of both neuronal- and glial-type clones. Like pp60c-src Lyn may be involved in a signalling pathway of neuroblasts committed to neuronal differentiation.
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PMID:Expression of the B cell-associated tyrosine kinase gene Lyn in primary neuroblastoma tumours and its modulation during the differentiation of neuroblastoma cell lines. 151 Jun 69

The differentiation pattern of two related human neuroblastoma cell lines, SK-N-SHF and SK-N-SHN, induced by retinoic acid and staurosporine was studied. Immunohistochemical and electron microscopic examination of the cells indicated that the SHF variant could undergo differentiation along a melanocytic route when treated with retinoic acid and to neuronal cells when treated with retionic acid and staurosporine together. Treatment of SHN cells with either or both these agents caused neuronal differentiation. The melanocytic pathway was characterized in part by the flattening of the cells, the appearance of melanocytic antigens and various forms of melanosomes, an increase in tyrosinase activity, and the absence of neuronal marker proteins. The neuronal route was typified by the development of long neuritic processes containing microtubules and numerous neurosecretory granules as well as by immunohistochemical reactions for neural cell adhesion molecule, synaptophysin, and neurofilament proteins. The significance of these results is discussed in terms of the differentiation responses of neuroblastoma cells to chemical agents as well as some of the factors involved in the regulation of phenotype expressions of these cells.
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PMID:Retinoic acid- and staurosporine-induced bidirectional differentiation of human neuroblastoma cell lines. 151 32

Expression of the N-myc oncogene is an important determinant of tumor behavior in human neuroblastoma. To study the regulation of N-myc, we have subcloned fragments of the 5' flanking region of the human N-myc gene upstream of the chloramphenicol acetyl transferase (CAT) reporter gene, and assayed for promoter activity in transient transfections into neuroblastoma and other cell lines. Upstream sequences were found to possess promoter activity to within 121 bp of the major cap site (-121). Negative regulatory elements were identified in regions approximately 2 kb and 500 bp upstream from the major cap site, as well as 150-1000 bp downstream. Promoter constructs containing downstream elements from bp +150 to +1000 were active in N-myc-expressing neuroblastoma cell lines, but not in non-expressing Epstein-Barr virus (EBV)-transformed 729-6 B-cell or HeLa cell lines, while those lacking this element were active in all cell types tested. All tested constructs retaining promoter activity showed decreased activity in parallel with the down-regulation of endogenous N-myc in response to treatment of transfected cells with retinoic acid. These studies suggest that N-myc regulation may be controlled at different levels, and provide a basis for further characterization of N-myc regulation in neuroblastoma.
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PMID:Cell type-specific expression and negative regulation by retinoic acid of the human N-myc promoter in neuroblastoma cells. 156 67

We have isolated a human neuroblastoma (NB) cell line, HTLA230, from the bone-marrow aspirate of a patient with stage-IV disease. Subcutaneous tumors after inoculation of HTLA230 cells into nude mice were composed of primitive neuroblasts which rarely contained neuro-secretory granules. Cytogenetic studies of the cell line demonstrated 2 distinct populations of cells with common chromosomal markers. Stable sub-clones with a differentiated or undifferentiated cell morphology were isolated, demonstrating phenotypical heterogeneity of the HTLA230 parental cell line. Treatment with retinoic acid (RA) induced extensive neurite outgrowth in the parental cell line and in phenotypically differentiated sub-clones, but rarely in undifferentiated ones. Long-term treatment with RA was not associated with down-modulation of mycN-gene expression, which could be achieved only in cultures treated additionally with aphidicolin, a DNA-synthesis inhibitor, thus eliminating growing NB cells. A RA resistant subclone (CI-5) was isolated from parental HTLA230 cells grown at clonal cell density. Cells originally showed a homogeneously differentiated morphology; however, flat cells (F-cells) appeared with time and were subsequently separately propagated. Transdifferentiation of isolated F-cells into cells with neuron-like (N-cell) morphology was observed. Immunohistochemical analysis demonstrated that F-cells had lost the expression of neuronal markers, including HNK-I and A2B5, and expressed the intermediate filament, vimentin. Furthermore, F-cells showed high incorporation of [methyl-3H] thymidine (3H-TdR) by autoradiography but no mycN protein could be detected, although present in the parental cell line. These results then suggest that the isolated NB cell line and the RA-resistant variant line represent an excellent in vitro model with which the bi-modal differentiation pathway of NB can be analyzed on a molecular biological level.
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PMID:Bi-modal differentiation pattern in a new human neuroblastoma cell line in vitro. 156 93


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