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

Neurotrophic factors have powerful effects on neuronal differentiation and the maintenance of neuronal phenotype, but understanding of their regulation of one important aspect of neuronal function, excitability, remains limited. We have examined the regulation of voltage-gated ion channels by two unrelated neurotrophic factors, NGF and ciliary neurotrophic factor (CNTF), in the SK-N-SH neuroblastoma cell line that is responsive to both factors. NGF and CNTF have strikingly different neuronal specificities and distributions in the nervous system, and might be expected to have significantly different effects on neuronal function. Using whole-cell, perforated-patch, and single-channel recording, we found that treatment with NGF increased levels of voltage-gated sodium, calcium, and potassium currents. In contrast, CNTF treatment increased levels of potassium currents only. NGF and CNTF appeared to regulate the same delayed-rectifier potassium current; in addition, NGF treatment resulted in increased levels of a second potassium current component. Such differential effects of neurotrophic factors on the expression of voltage-gated ion channels would have profound effects on the excitability of target neurons in vivo.
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PMID:Regulation of voltage-gated ion channels by NGF and ciliary neurotrophic factor in SK-N-SH neuroblastoma cells. 752 28

Growth factors can induce both proliferation or differentiation of neuroblastoma (NB) cells through interaction with specific receptors. Using two automated colorimetric assays for determinations of cell numbers, the present study demonstrates that a) different NB and neuroepithelioma cell lines show distinct responses, both qualitatively and quantitatively, to basic FGF (bFGF), NGF, and EGF; b) even closely related NB cell lines (e.g., SK-N-SH, SH-SY5Y, and SHEP) do not respond uniformly to these factors; c) responses of the two neuroepithelioma cell lines employed (SK-N-MC and CHP-100) differ, but match those of certain NB cell lines; and d) two growth factors, bFGF and EGF, may both stimulate or inhibit proliferation, depending on the cell line studied. Specifically, IMR-32, SK-N-SH, and SH-SY5Y showed a mitogenic response to each growth factor. Maximal proliferative responses ranged from 204-355% as compared to controls (100%). GICAN was stimulated by NGF (199%), and SK-N-MC and NMB by EGF (282 and 140%, respectively), but other factors were ineffective. CHP-100 and GIMEN were inhibited by bFGF. NGF and EGF were not effective on CHP-100 cells, while EGF caused an arrest of mitogenic activity in GIMEN cells, and NGF stimulated their proliferation. Cell lines SHEP and LAN1 did not respond to any factor. To begin to analyze putative relationships of growth factor responsiveness and growth factor/growth factor receptor expressions, IMR-32, GIMEN, and LAN1 cell lines were studied for the presence of bFGF, NGF, FGF receptors (R)-1 (flg) and FGFR-4, trk, and low-affinity NGF receptor (p75) mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterogeneity of human neuroblastoma cell lines in their proliferative responses to basic FGF, NGF, and EGF: correlation with expression of growth factors and growth factor receptors. 762 87

In Alzheimer's disease, Tau proteins are abnormally phosphorylated. In this paper, we describe a cellular model producing such pathological Tau proteins. After differentiation by NGF and treatment with okadaic acid (an inhibitor of phosphatases 1 and 2 A), neuroblastoma SKNSH-SY 5Y cells produced Tau proteins with an increased apparent molecular weight and a more acidic isoelectric point when compared to Tau proteins from control cells. These modified tau proteins bore Alzheimer-type epitopes detectable by antibodies specific to phosphorylated Alzheimer epitopes. This model is the first step toward a pharmacological approach of neuroprotection.
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PMID:[Detection of Alzheimer type pathological epitopes on Tau proteins of neuroblastoma cells after treatment with okadaic acid]. 769 12

Hypoxanthine/guanine phosphoribosyl transferase (HPRT)-deficient cell lines, designated as Neuro-2aTG and PC12TG, were established from mouse neuroblastoma Neuro-2a and rat pheochromocytoma PC12, respectively. Both cell lines stably exhibited HPRT- phenotype, and expressed neuronal properties, i.e., constitutive expression of 200-kD neurofilament protein in Neuro-2aTG and responsiveness to NGF in PC12TG. Therefore, these cell lines will be useful as fusion partners in somatic cell hybridization with neurons.
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PMID:Establishment of HPRT-deficient cell lines from mouse neuroblastoma Neuro-2a and rat pheochromocytoma PC12. 776 25

There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study gene regulation during differentiation, N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment. It was found that cell lines which expressed N-myc did not express c-myc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression. In NGF-induced differentiated neuroblastoma cells, c-myc oncogene was down-regulated in comparison with the control samples. The time course of c-myc down-regulation was concomitant with the appearance of morphological differentiation. In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells. These results indicate that down-regulation of c-myc oncogene may be a key event during NGF-induced differentiation and over-expression of c-myc oncogene may, at least partially, be responsible for the genesis of neuroblastoma.
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PMID:Down-regulation of c-myc oncogene during NGF-induced differentiation of neuroblastoma cell lines. 786 34

Information on the transmembrane signaling events and subsequent biochemical processes initiated by ciliary neurotrophic factor (CNTF) receptor activation in neurons is lacking. SH-SY5Y cells, a human neuroblastoma cell line expressing CNTF receptors, were used to study metabolic changes associated with functional ligand-receptor interactions. Real-time measurements quantifying the rate of extracellular acidification by SH-SY5Y cells (a measure of metabolic activity) were made using a silicon-based cytosensor. Application of recombinant human CNTF (rhCNTF) to resting SH-SY5Y cells increased their acidification rate in a concentration and time-dependent manner with an apparent EC50 of 60 ng/ml. Pretreatment of cells with phosphatidylinositol-specific phospholipase C (PI-PLC) prevented the CNTF, but not an NGF-stimulated increase in acidification rate. Collectively, these results demonstrate that: (1) SH-SY5Y cells express functional CNTF receptors; and (2) the initial signal transduction mechanism activated by the CNTF receptor in SH-SY5Y cells is distinct from that activated by the NGF receptor; however, both may ultimately stimulate the same downstream biochemical messengers to increase cellular metabolism.
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PMID:Recombinant human ciliary neurotrophic factor stimulates the metabolic activity of SH-SY5Y cells as measured by a cytosensor microphysiometer. 806 84

The C6 glial cell line has been used as a model cell system for the investigation of new glial produced neurotrophic and neurotropic molecules. By using the C6 cell line grown in a defined medium on collagen, this laboratory has isolated a distinct neurite promoting factor (NPF) that is potentiated by the presence of collagen (CPNPF). We have observed that C6 cells cultured in a defined medium on collagen (rat type-I) slowed their growth rate and expressed an astrocytic- or oligodendrocytic-like morphology. CPNPF, at this state of purity, appears to be a distinct NPF which induces neurite outgrowth (neurites of 1 or more somal diameters) in PC12 cells. These neurite promotion effects, however, appear to support the neuron morphology for only a short period (4 days) of time without the presence of neurotrophic factor (NTF). The neurite promoting activity is ineffective in inducing neurite outgrowth using mouse neuroblastoma cells (neuro-2a). CPNPF appears to be a heat stable protein whose activity does not depend on the presence of intact collagen, heparin sulfate proteoglycan (HSPG), or chondroitin sulfate proteoglycan (CSPG). Exposure to dissociative conditions results in a loss of neurite promoting activity. CPNPF is not a glycoprotein that contains an accessible alpha-D-mannopyranosyl, alpha-D-glucopyranosyl, or a sterically related residue (hydroxyl groups in the C-3,4, and 5 positions). Although these residues are not present on all glycoproteins, it does indicate that CPNPF is most likely not a glycoprotein. CPNPF activity is not blocked by neutralizing antibodies directed toward NGF, beta-FGF, IL-1 beta, IL-6, TGF-beta 2, TGF-beta 1.2, TGF-beta 3, TGF-beta 5, or EGF. CPNPF appears to either be oligomeric protein or a complex of proteins. On the basis of indirect evidence, it does not appear to be glial derived protease nexin-I. The alteration in morphology of the C6 glial cell line by serum-free conditions in the presence of collagen may have induced the production of a potentially new NPF not seen by previous investigators.
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PMID:Identification of a collagen potentiated neurite promoting factor isolated from C6 glioma cells. 836 Sep 47

Neuroblastoma (NB), a neural crest derived tumor in children, shows a characteristic pattern of dissemination that includes adrenal glands, local lymph nodes, bone, liver, skin, and bone marrow. We have reconstructed a similar metastatic pattern in SCID mice following tail vein injection of human NB cells. HTLA230, an NB cell line isolated from a patient with advanced disease, and its NGF receptor (trkA) expressing derivative (18-10) cells, consistently disseminated to the liver, the adrenal gland, and the bone marrow, but not the lungs. Metastases in the different organs showed a characteristic hemorrhagic histopathology, and tumors in the bone marrow presented as syncytia-like cell aggregates, typically seen in patients. Cell lines reestablished from 18-10 derived liver and bone marrow metastases maintained their cellular morphology, growth behavior, N-myc overexpression, trkA expression, and functionally responded to NGF treatment, leading to growth arrest and neurite outgrowth. Hence circulating human NB cells in SCID mice show a similar organ-specific metastatic potential as seen in patients, independent of trkA expression.
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PMID:A metastatic neuroblastoma model in SCID mice. 870 12

Neurons and glia are capable of both secreting and responding to a large variety of growth factors. However, information on multiple expression of growth factors and their receptors was usually obtained from uncorrelated observations, using cells from various animals of origin, developmental stages, growth phases, culture ages and culture conditions. Because of its specificity and extreme sensitivity, reverse transcription-polymerase chain reaction (RT-PCR) is uniquely suitable to study a large panel of growth factors and their receptors from a limited cell sample, free of these intervening variables. In this paper we evaluate the expression of mRNA of a total of 35 growth factor-related proteins by conducting RT-PCR on three neuronal cell lines: the PC12 rat pheochromocytoma line, the MAH rat sympathoadrenal progenitor line, and the N18 mouse neuroblastoma line. Three types of results are presented. The first confirms the existing knowledge such as the presence of Trk-A (NFG receptor) in PC12. The second consists of new information that expands and extends earlier observations, such as the presence of CNTF receptor complex in PC12, which explains our previous report that CNTF enhances the biological effects of NGF on these cells. The third consists of novel information that leads the way to further experimentation by the more conventional methods. These include the strong expression of Trk-B by MAH, predicting the biological responsiveness of MAH to BDNF and NT-4, and the expression of CNTF receptor in N18. Our results also suggest that CNTF is an autocrine factor for PC12 and MAH, since both lines express the growth factor as well as the receptor. Thus, RT-PCR is a valuable tool in growth factor research that can be used in complement to, and interactively with, other approaches such as bioassay, receptor binding, and immunochemical determination. It will be particularly useful for screening a large number of growth factors in minute areas of the brain in patients suffering from neurodegenerative diseases such as Parkinson's and Alzheimer's.
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PMID:Expression of mRNAs of multiple growth factors and receptors by neuronal cell lines: detection with RT-PCR. 878 8

This study has shown that glycosaminoglycans added to the culture medium may affect neurite formation in SH-SY5Y neuroblastoma cells. The most effective glycosaminoglycans are heparin and COS 8, a preparation with low anticoagulant activity. Promotion of neuritogenesis was remarkable at concentrations as low as 10(-8) and 10(-10). When added at 10(-4) M both agents are inhibitory. Chondroitin-4 sulfate, dermatan sulfate, and heparan sulfate were also effective, the doses required were, however, as high as 10(-4) M for promoting and 10(-4) M for inhibiting neuritogenesis. Thereby low doses of glycosaminoglycans promote, while higher doses inhibit neurite formation. The effects were observed when neuritogenesis was promoted in neuroblastoma cultures either by deprivation of serum or by addition of retinoic acid, in the former case neuritogenesis occurred within 48 hr; in the latter, in 14 days. PC12 pheochromocytoma cells neuritogenesis was triggered by adding NGF to the culture medium. We have also observed that glycosaminoglycan supplementation to the culture medium lowered the quantity of NGF required to form neurites by PC12 cells. Glycosaminoglycans at the dose of 10(-8) M allow the formation of PC12 neurites even in presence of 1 ng/ml NGF, a dose that normally is ineffective.
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PMID:Glycosaminoglycans in nerve injury: 1. Low doses of glycosaminoglycans promote neurite formation. 895 68


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