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

The F11 cell line is a fusion product of cells of mouse neuroblastoma cell line N18TG-2 with embryonic rat dorsal-root ganglion (DRG) neurons. Previous biochemical results suggest that they express mu- and delta-opioid receptors that are negatively coupled to adenylate cyclase. The present study provides direct agonist-binding and electrophysiologic evidence of mu and delta, but not kappa, receptor expression in F11 cells. Radioligand binding assays show that F11 cell membranes bind the mu- and delta-opioid receptor agonists, DAGO and DPDPE with Kd = 4.5 and 4.9 nM and Bmax = 111 and 195 fmol/mg, respectively. Tight-seal patch-clamp recordings of F11 cells after several days in a differentiating culture medium (low serum, cyclic AMP and nerve growth factor) showed that: (i) the outward K+ current during pulsed depolarization in most of these cells was increased by either DAGO or DPDPE, but none were responsive to both opioids or to the kappa-opioid receptor agonist, U-50,488H. The response was blocked by relevant receptor antagonists, naloxone, beta-funaltrexamine or naltrindole; (ii) cells without processes responded neither to DAGO nor to DPDPE; (iii) treatment with pertussis toxin blocked all opioid-induced increases in outward K+ current. The opioid-induced increase in voltage-dependent membrane K+ current in F11 cells resembles the inhibitory effect elicited by mu- and delta-opioid agonists in primary cultures of mouse DRG neurons.
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PMID:F11 neuroblastoma x DRG neuron hybrid cells express inhibitory mu- and delta-opioid receptors which increase voltage-dependent K+ currents upon activation. 133 Feb 16

We have previously proposed that polysialic acid (PSA), which is attached to NCAM on the cell surface, can serve to regulate a variety of cell-cell interactions. The present study provides evidence that hydrated PSA influences a sufficiently large volume at the cell surface to exert broad steric effects, and that the removal of PSA in fact causes a detectable change in intercellular space. Using F11 neuron/neuroblastoma hybrid cells as a model system, the measured density and size of PSA suggests that a substantial fraction of the space between two apposed cell surface membranes could be sterically influenced by the presence of PSA. Specific enzymatic removal of PSA, which is similar in magnitude to changes that occur in many tissues during normal development, caused about a 25% decrease in the distance between two apposed cells. By contrast, removal of both heparan sulfate and chondroitin sulfate from the cells had no effect on this parameter. It is proposed that such changes in membrane-membrane distance could serve to alter selectively the efficiency of encounter between complementary receptors on apposing cells, and explain at least in part the broad biological influences of PSA.
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PMID:Intercellular space is affected by the polysialic acid content of NCAM. 154 38

Subclones of F11 neuronal hybrid cells (neuroblastoma x dorsal root ganglion neurons) have segregated differing and/or overlapping neuritogenic mechanisms on three substrata--plasma fibronectin (pFN) with its multiple receptor activities, cholera toxin B subunit (CTB) for binding to ganglioside GM1, and platelet factor-4 (PF4) for binding to heparan sulfate proteoglycans. In this study, specific cell surface receptor activities for the three substrata were tested for their modulation during neuritogenesis by several experimental paradigms, using F11 subclones representative of three differentiation classes (neuritogenic on pFN only, on CTB only, or on all three substrata). When cycloheximide was included in the medium to inhibit protein synthesis during the active period, neurite formation increased significantly for all subclones on all three substrata, virtually eliminating substratum selectivity for differentiation mediated by cell surface integrin, ganglioside GM1, or heparan sulfate proteoglycans. Therefore, one or more labile proteins (referred to as disintegrins) must modulate functions of matrix receptors (e.g., integrins) mediating neurite formation. To verify whether cycloheximide-induced neuritogenesis was also regulated by integrin interaction with cell surface GM1, two approaches were used. When (Arg-Gly-Asp-Ser)-containing peptide A was added to the medium, it completely inhibited cycloheximide-induced neuritogenesis on all three substrata of all subclones, indicating stringent requirement for cell surface integrin function in these mechanisms. In contrast, when CTB or a monoclonal anti-GM1 antibody was also added to the medium, cycloheximide-induced neuritogenesis was amplified further on pFN and sensitivity to peptide A inhibition was abolished. Therefore, in some contexts ganglioside GM1 must complex with integrin receptors at the cell surface to modulate their function. These results also indicate that (a) cycloheximide treatment leads to loss of substratum selectivity in neuritogenesis, (b) this negative regulation of neurite outgrowth is affected by integrin receptor association with labile regulatory proteins (disintegrins) as well as with GM1, and (c) complexing of GM1 by multivalent GM1-binding proteins shifts neuritogenesis from an RGDS-dependent integrin mechanism to an RGDS-independent receptor mechanism.
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PMID:Neurite outgrowth in dorsal root neuronal hybrid clones modulated by ganglioside GM1 and disintegrins. 182 96

Clones of F11 hybrid (neuroblastoma X dorsal root neuron) cells have been tested for adherence and neurite outgrowth on three different substrata on which the parental cells display some competence--plasma fibronectin (pFN) with its multiple receptors, cholera toxin subunit B(CTB) as a model ganglioside GM1-binding substratum, and platelet factor-4 (PF4) as a model proteoglycan-binding substratum. This paradigm tests for independently segregating and overlapping mechanisms of neuritogenesis via transmembrane processes in pluripotent hybrid cells based on random loss of chromosomes contributed by the parent neural cells. For the nine clones tested, attachment was significantly lower on CTB but much higher on PF4 for all clones when compared to their attachment on pFN. Supplementation of cells with GM1 stimulated attachment of only two clones (on all three substrata). Neurite outgrowth was observed in a substratum-specific pattern and varied from 0 to greater than 60% on pFN; on CTB and PF4 substrata, the patterns were similar to each other but differed markedly from the pattern on pFN. In contrast, PF4- and CTB-directed neurites differed morphologically from each other while sharing some characteristics with neurites on pFN. Supplementation with GM1 or GT1b, but not GD1a, was inhibitory for neurite outgrowth in certain clones. Cycloheximide pretreatment distinguished several classes of clones based on inhibition of neuritogenesis. While most clones on pFN were unaffected, all clones on CTB and PF4 displayed significant and comparable degrees of inhibition, suggesting the sharing of some protein intermediate(s) on these substrata. Exposure to cycloheximide only during the active period of neuritogenesis generated higher percentages and longer neurites for all clones, indicating a widely-used negative regulation mechanism. Based on substratum type and cycloheximide protocols, these data have resolved six or more different transmembrane signalling processes for generating different classes of neurites. Some mechanisms have been segregated into individual clones while others overlap in other clones, providing cell systems for biochemical and molecular biological dissection of these processes.
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PMID:Clonal segregation of multiple and overlapping matrix adhesive responses in dorsal root neuronal derivative cells. 233 51

Some neuron-derived cells, such as neuroblastoma cells, adhere and extend neurites on fibronectin (FN) substrata by processes that can be independent of binding to the Arg-Gly-Asp-Ser sequence (RGDS in FN) and independent of proteoglycan/ganglioside-binding activities of FN. Proteolytic fragments of various FNs have been used in this study to map a new adhesion-promoting domain in FNs that may be neural cell-specific. A thermolysin-generated fragment of human plasma FN (F110 containing the RGDS domain) or the analagous fragment from transformed human cell FN (F120, also containing the alternately spliced extra domain b[EDb]) facilitate RGDS-independent adherence and neurite extension of human neuroblastoma cells and an F11 hybrid neuronal line (by fusion of mouse neuroblastoma cells with rat dorsal root ganglion neurons) as effectively as adherence and neurite extension on intact FN. Since neither F110 nor F120 contains sequences from the alternately spliced IIICS region of FN, neurite-promoting activity in these fragments cannot be ascribed to a recently discovered cell-binding domain in this region. Furthermore, F120 could be cleaved into two subfragments retaining virtually all the sequence of the parent fragment: F35 from the C terminus of F120 containing the RGDS domain, and F90 from the N terminus containing most of the EDb region bordering the thermolysin cleavage site. These neuronal cells could adhere but not extend neurites on substrata coated with either F35 or F90 alone while 3T3 cells could adhere only on F35. Mixtures of F35 and F90 on substrata could reconstitute some, but not nearly all, of the neurite-promoting activity of F120. Therefore, these data identify a new cell-binding domain in common sequences of FNs on the N-terminal side of EDb and demonstrate cooperativity between this RGDS-independent domain and the RGDS-dependent domain for maximal differentiation of these neuron-derived cells. Several possibilities for a receptor directed to this new domain are discussed.
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PMID:Requirement for two different cell-binding domains in fibronectin for neurite extension of neuronal derivative cells. 235 3

Attachment and neurite extension processes have been evaluated for an immortalized derivative cell of a rat dorsal root neuron after fusion with a mouse neuroblastoma cell (the clonal F11 hybrid cell line) and these processes compared with previous studies of neuroblastoma cells, since both cell types may be derived from the neural crest of the developing embryo. Biochemically defined substrata were provided by human plasma fibronectin (pFN), the heparan sulfate-binding protein platelet factor-4 (PF4), and the ganglioside GM1-binding protein cholera toxin B subunit (CTB). While some attachment of unsupplemented cells was noted on CTB substrata, GM1 supplementation permitted F11 cells to attach as well on CTB as on pFN or PF4. On PF4, very few neurite processes were observed while on pFN two morphologically distinct types of neurites could be identified: short, linear processes in a low percentage of cells resembling those of neuroblastoma cells and long, irregular and narrow processes in a higher percentage of cells resembling those of dorsal root neurons. On CTB, neurites of the latter class were even more prominent; however, cell bodies on CTB failed to spread by cytoplasmic extension as commonly observed in F11 cells on pFN and, to some extent, on PF4. The formation of both neurite classes on either pFN or CTB was completely inhibited by low concentrations of an RGDS (Arg-Gly-Asp-Ser) peptide in the medium of cultures, indicating the significance of pFN's binding to cell surface integrin or ganglioside GM1's possible interaction with integrin for mediating the differentiative process. In contrast, neurite formation of neuroblastoma cells is refractile to the soluble peptide as reported previously. Neurite extensions of F11 cells on either pFN or CTB were comparably sensitive to low concentrations of cytochalasin D, revealing the mediation of microfilament reorganization in these processes. Treatment of F11 cells with cycloheximide failed to inhibit neurite extension on pFN but did partially inhibit extension on CTB; this contrasts with the very high sensitivity of neurite formation by neuroblastoma cells on CTB substrata reported previously.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple and alternative adhesive responses on defined substrata of an immortalized dorsal root neuron hybrid cell line. 316 39

Immunoprecipitation studies with application of monoclonal antibody F11 originally made to a partially purified spent medium antigen of melanoma cells, made it possible to delineate the molecular profiles of both the cell associated and spent medium antigens recognized on melanoma cells intrinsically labeled with glycoprotein precursors. F11 distinguishes a glycoprotein of Mr 100,000 (100 K) in the spent media of melanoma cells while a parallel analysis of detergent lysates of cells reveals a pattern of three glycoproteins of Mr 75, 77, and 100 K. Pulse-chase analysis of the biosynthesis of these antigens indicated that F11 first recognizes the 75 and 77 K antigens in the absence of a 100K component suggesting strongly that these molecules contain an antigenic site recognized by F11. The 100 K antigen appears later in the pulse-chase analysis with kinetics that suggest some of the 75 and 77 K antigens are biosynthetic precursors of the 100 K antigen. This molecule is ultimately secreted into the extracellular media and appears to be a sialoglycoprotein judging from its sensitivity to neuraminidase. A cross-reactive species with an approximate Mr 90 K is also recognized by F11 in indirect immunoprecipitation analysis of spent media from a neuroblastoma cell line indicating that a common antigenic site exists on this secreted but structurally different neuroblastoma antigen. Thus, a combination of immunochemical and biosynthetic analyses of cell-associated and secreted antigens recognized by monoclonal antibody F11 demonstrate such molecules can differ structurally when isolated from the same or different tumor cells. These findings indicate the necessity to establish molecular profiles of melanoma-associated glycoprotein antigens recognized by monoclonal antibodies to characterize and define their potential biological functions within tumor cells.
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PMID:Immunochemical and biosynthetic analysis of monoclonal antibody-defined melanoma-associated antigen. 620 29

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.
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PMID:PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas. 810 13

We have prepared a monoclonal antibody, Neuro-1, that recognizes the human homolog of the chicken contactin/F11 and mouse F3 cell adhesion molecules. The Neuro-1 antigen, structurally characterized as a 135 kDa glycosylphosphatidylinositol-linked glycoprotein, was immunoaffinity purified and partially sequenced. Comparison of an internal peptide sequence to that predicted from the chicken contactin/F11, mouse F3 and human contactin (reported herein) cDNA sequence identifies the Neuro-1 antigen as human contactin. Moreover, a polyclonal antisera generated against the purified Neuro-1 antigen was immunoreactive with a fragment of human contactin expressed in bacteria. The complete coding and deduced amino acid sequences of human contactin were determined and are 86% and 95% identical to the respective mouse F3 sequences. Structural features shared with contactin/F11/F3 include six immunoglobulin type C2 and four fibronectin type III-like domains, multiple sites for asn-linked glycosylation and a COOH-terminal signal peptide presumably removed during the generation of a phosphatidylinositol cell surface linkage. The potential for glycosylation and GPI-linkage is also consistent with protein chemical studies of human contactin. Contactin mRNA expression was characterized using Northern blot analyses of human tissues and cell lines. High level expression of a single contactin transcript in adult brain, and low level expression of multiple transcripts in lung, pancreas, kidney and skeletal muscle are observed. Highly expressed multiple transcripts, similar in pattern to that of pancreas, lung, kidney and skeletal muscle, are also observed in human neuroblastoma and retinoblastoma cell lines.
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PMID:Identification and characterization of the human cell adhesion molecule contactin. 816 10

In a previous study, we showed that microM concentrations of mu or delta opioid agonists increase voltage-dependent outward K+ currents in neuroblastoma x DRG neuron hybrid F11 cells via pertussis toxin-sensitive receptors. The present study demonstrates that much lower concentrations (fM to nM) of these opioids (DAGO and DPDPE) decreased voltage-dependent outward K+ currents during step depolarization. The opioid antagonist, naloxone (3 nM) prevented these decreases in K+ current as did the cholera toxin subunits A or B (ca. 1 nM). Furthermore, the specific mu opioid receptor antagonist, beta-funaltrexamine (5 nM) blocked the decrease by DAGO and the specific delta antagonist, naltrindole (1 nM) blocked that by DPDPE. Acute GM1 ganglioside (1 microM) treatment markedly enhanced the efficacy of opioid-induced decrease in K+ current. After treating the cells with pertussis toxin (1 microgram/ml) for 2 days or more, these opioids decreased the K+ current even when tested at concentrations as high as 1 microM. These results indicate that the decrease in K+ current elicited in F11 cells by low concentrations of mu and delta opioid agonists resembles the opioid-induced prolongation of the action potential duration and decrease in voltage-dependent K+ conductance that occur in DRG neurons in primary cultures. The F11 cell line provides therefore a valuable model system for correlative pharmacologic, electrophysiologic and biochemical analyses of Gs-coupled, GM1 ganglioside-regulated excitatory opioid receptor functions, in addition to G(i)/G(o)-coupled inhibitory receptor functions, in sensory neurons.
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PMID:mu and delta opioid agonists at low concentrations decrease voltage-dependent K+ currents in F11 neuroblastoma x DRG neuron hybrid cells via cholera toxin-sensitive receptors. 838 68


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