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)

Nerve growth factor (NGF) is important to the survival, development, and differentiation of neurons. Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR). In this study, NGFR expression by human fetal and adult adrenal medullary tissue, peripheral nervous system (PNS) neuroectodermal tumors (neuroblastoma, ganglioneuroblastoma, ganglioneuroma), pediatric primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), and CNS gliomas was examined by an immunohistochemical technique. Sixty-nine tumors in total were probed in this manner. Nerve growth factor receptor immunoreactivity was confined to nerve fibers and clusters of primitive-appearing cells in the fetal adrenal, and to nerve fibers and ganglion cells of the adult adrenal medulla; adrenal chromaffin cells were negative. In PNS neuroectodermal tumors, there was NGFR expression in tumor cells of 6 of 11 neuroblastomas and 6 of 6 ganglioneuroblastomas or ganglioneuromas. Thirteen of thirty-five CNS PNETs showed NGFR positivity. In most CNS PNETs, NGFR was restricted to scattered single or small groups of cells, but two tumors with astroglial differentiation showed much more extensive immunoreactivity. Most astrocytomas (11 of 14) and all ependymomas (3 of 3) were intensely NGFR positive.
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PMID:Nerve growth factor receptor expression in peripheral and central neuroectodermal tumors, other pediatric brain tumors, and during development of the adrenal gland. 164 53

The neu oncogene encodes a 185-kDa transmembrane glycoprotein tumor antigen, termed p185. We have recently described a monoclonal antibody reactive with a cell surface domain of the p185 molecule. In vivo treatment with this anti-p185 monoclonal antibody was able to significantly inhibit the tumorigenic growth of neu-transformed NIH 3T3 cells implanted into nude mice. Such treatment had no effect on the tumorigenic growth of Ha-ras-transformed NIH 3T3 cells. Furthermore, anti-p185 antibody treatment was able to inhibit the growth of the rat neuroblastoma cells from which the neu oncogene was initially isolated. These results demonstrate that a monoclonal antibody reactive with the extracellular domain of an oncogene-encoded protein can exert a significant antitumor effect; such antibodies may prove useful in the therapy of certain malignancies.
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PMID:Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. 346 78

The occurrence of multidrug resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. MDR cell lines are resistant to the so-called naturally occurring anti-cancer drugs, such as anthracyclines, Vinca alkaloids and epipodophyllotoxins, but are not cross-resistant to alkylating agents, antimetabolites and cisplatin. So far, three separate forms of MDR have been characterized in more detail: classical MDR, non-Pgp MDR and atypical MDR. Although all three MDR phenotypes have much in common with respect to cross-resistance patterns, the underlying mechanisms certainly differ. Atypical MDR is associated with quantitative and qualitative alterations in topoisomerase II alpha, a nuclear enzyme that actively participates in the lethal action of cytotoxic drugs. Atypical MDR cells do not overexpress P-glycoprotein, and are unaltered in their ability to accumulate drugs. In this review we will focus on classical and non-Pgp MDR. The molecular mechanism of classical and non-Pgp MDR is transcriptional activation of membrane-bound transport proteins. These transport proteins belong to the ATP-binding cassette (ABC) superfamily of transport systems. The classical MDR phenotype is characterized by a reduced ability to accumulate drugs, due to activity of an energy-dependent uni-directional, membrane-bound, drug-efflux pump with broad substrate specificity. The classical MDR drug pump is composed of a transmembrane glycoprotein (P-glyco-protein-Pgp) with a molecular weight of 170 kD, and is, in man, encoded by the so-called multidrug resistance (MDR1) gene. Typically, non-Pgp MDR has no P-gly-coprotein expression, yet has about the same cross-resistance pattern as classical MDR. This non-Pgp MDR phenotype is caused by overexpression of the multidrug resistance-associated protein (MRP) gene, which encodes a 190 kD membrane-bound glycoprotein (MRP). MRP probably works by direct extrusion of cytotoxic drugs from the cell and/or by mediating sequestration of the drugs into intracellular compartments, both leading to a reduction in effective intracellular drug concentrations. For the classical MDR phenotype, evidence is accumulating that it plays a role indeed, in clinical drug resistance, especially in some hematological malignancies (acute myeloid leukemia, multiple myeloma and non-Hodgkin's lymphoma) and solid tumors (soft tissue sarcomas and neuroblastoma). The association of MRP with clinical drug resistance has not been elaborated, yet, and studies on MRP expression in human cancer have just begun. We found that overexpression of MRP, as determined by RNase protection assay as well as by immunohistochemistry, occurs in several human cancers, among which are cancer of the lung, esophagus, breast and ovary, and leukemias. Further studies are indicated to establish whether elevated MRP expression at diagnosis is an unfavorable prognostic factor for clinical outcome of chemotherapy.
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PMID:Molecular mechanisms of multidrug resistance in cancer chemotherapy. 888 Aug 78

Paranodin/contactin-associated protein (caspr) is a transmembrane glycoprotein of the neurexin superfamily that is highly enriched in the paranodal regions of myelinated axons. We have investigated the role of its association with F3/contactin, a glycosylphosphatidyl inositol (GPI)-anchored neuronal adhesion molecule of the Ig superfamily. Paranodin was not expressed at the cell surface when transfected alone in CHO or neuroblastoma cells. Cotransfection with F3 resulted in plasma membrane delivery of paranodin, as analyzed by confocal microscopy and cell surface biotinylation. The region that mediates association with paranodin was mapped to the Ig domains of F3 by coimmunoprecipitation experiments. The association of paranodin with F3 allowed its recruitment to Triton X-100-insoluble microdomains. The GPI anchor of F3 was necessary, but not sufficient for surface expression of paranodin. F3-Ig, a form of F3 deleted of the fibronectin type III (FNIII) repeats, although GPI-linked and expressed at the cell surface, was not recovered in the microdomain fraction and was unable to promote cell surface targeting of paranodin. Thus, a cooperative effect between the GPI anchor, the FNIII repeats, and the Ig regions of F3 is required for recruitment of paranodin into lipid rafts and its sorting to the plasma membrane.
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PMID:The glycosylphosphatidyl inositol-anchored adhesion molecule F3/contactin is required for surface transport of paranodin/contactin-associated protein (caspr). 1076 38

CD44 is a polymorphic transmembrane glycoprotein that exists as multiple isoforms resulting from alternative splicing and posttranslational modifications. Enhanced expression of CD44 has been correlated to the tumorigenicity and metastatic behavior in different malignant tumors. In contrast, human neuroblastomas exhibit an inverse correlation between CD44 expression and tumor malignancy. To determine whether there is a CD44 silencing in sympatho-adrenal precursors as a possible explanation for the down-regulation of CD44 in neuroblastomas, the expression of standard CD44H and v6, v7, v7v8, or v10 isoforms was analyzed by immunohistochemistry in human adrenal glands of 14- to 20-week-old gestational age fetuses. All of the fetal neuroblasts localized in the adrenal gland parenchyma and migrating from the sympathetic nerve chain into the fetal adrenal cortex strongly expressed CD44H but none of the CD44 isoforms could be detected in these cells. In contrast, a strong expression of CD44v7 and v6 was detected in the fetal adrenal cells. These results indicate that, as for many other cell types, the CD44H expressed by fetal neuroblasts may contribute to controlling their migration into the adrenal medulla and that the down-regulation of CD44H in neuroblastoma cells should be explained by mechanisms other than the fetal suppression of CD44H expression in their normal counterparts.
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PMID:Expression of CD44 and its isoforms in the fetal neuroblasts. 1139 37

The transmembrane glycoprotein teneurin 2 is expressed by neurons in the developing avian thalamofugal visual system at periods that correspond with target recognition and synaptogenesis. Partial and full-length teneurin 2 constructs were expressed in cell lines in vitro. Expression of the cytoplasmic domain is required for the induction of filopodia, the transport of teneurin 2 into neurites and the co-localization of teneurin 2 with the cortical actin cytoskeleton. In addition, expression of the extracellular domain of teneurin 2 by HT1080 cells induced cell aggregation, and the extracellular domain of teneurin 2 became concentrated at sites of cell-cell contact in neuroblastoma cells. These observations indicate that the homophilic binding of teneurin 2 may play a role in the development of specific neuronal circuits in the developing visual system.
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PMID:Teneurin 2 is expressed by the neurons of the thalamofugal visual system in situ and promotes homophilic cell-cell adhesion in vitro. 1236 62

Nicastrin is a type 1 transmembrane glycoprotein that interacts with presenilin, Aph-1, and Pen-2 proteins to form a high molecular complex with gamma secretase activity. Then, nicastrin has a central role in presenilin-mediated processing of beta-amyloid precursor protein and in some aspects of Notch/glp-1 signaling in vivo. Here, we isolated a rat nicastrin cDNA and investigated gene expression in embryonic and adult rat tissues. The predicted amino acid sequence is comprised of 708 residues and showed a high degree of identity with other vertebrate orthologs. Besides full-length nicastrin mRNA, we identified an alternative spliced variant lacking the whole exon 3 and predicted to encode a 62-residue-long truncated protein. Full-length nicastrin mRNA was observed to be ubiquitously expressed, while the spliced variant was preferentially transcribed in the nervous system, whether in embryonic or adult neural tissues. Studies performed on primary cell cultures demonstrated that the short isoform was expressed in neurons, but not in astrocyte and microglial cells. Further experiments performed to verify the presence of the variant in neuroblastoma culture failed to show any truncated protein. Treatments by cyclohexamide showed the involvement of a quality control-based surveillance mechanism, which selectively degrades the exon 3-skipped isoform. In summary, this is the first report describing a novel skipped isoform of nicastrin which may suggest a new possible control mechanism based on the alternative splicing and nonsense-mediated mRNA decay to regulate brain protein expression and provide newer insights into potential implication in Alzheimer's disease.
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PMID:Rat nicastrin gene: cDNA isolation, mRNA variants and expression pattern analysis. 1589 82

Human CD38 antigen is a 42-45 kDa type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long C-terminal extracellular region. It is widely expressed in different cell types including thymocytes, activated T cells, and terminally differentiated B cells (plasma cells) and it is involved in cellular proliferation and adhesion. CD38 acts as an ectocyclase that converts NAD+ to the Ca2+ -releasing second messenger cyclic ADP-ribose (cADPR). It has been also demonstrated that increased extracellular levels of NAD+ and cADPR are involved in inflammatory diseases and in cellular damage, such as ischemia. In the present study, we have characterized the expression of CD38 in human neuroblastoma SH-SY5Y cell line. All-trans-retinoic acid (ATRA) treatment was used to induce cell differentiation. Our results indicate that: a) even if SH-SY5Y cells have a negative phenotype express CD38 at nuclear level, ATRA treatment does not influence this pattern; b) CD38 localizing to the nucleus may co-localize with p80-coilin positive nuclear-coiled bodies; c) purified nuclei, by Western blot determinations using anti-CD38 antibodies, display a band with a molecular mass of approximately 42 kDa; d) SH-SY5Y cells show nuclear ADP-ribosyl cyclase due to CD38 activity; e) the basal level of CD38 mRNA shows a time-dependent increase after treatment with ATRA. These results suggest that the presence of constitutive fully functional CD38 in the SH-SY5Y nucleus has some important implications for intracellular generation of cADP-ribose and subsequent nucleoplasmic calcium release.
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PMID:Expression of CD38 in human neuroblastoma SH-SY5Y cells. 1833 35

Expression of CD44, a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions, has been associated with growth and metastatic behavior in several malignant tumors. In contrast to most other malignancies, in which up-regulation of CD44 is related to tumor progression, the absence of CD44 expression characterizes the aggressiveness of neuroblastomas in clinical studies. In this study, cells of human neuroblastoma cell lines (IMR-32, Kelly, LAN-1, LAN-5, LS, SH-SY5Y and SK-N-SH) were injected subcutaneously into SCID mice, and their growth behavior and CD44 expression were analyzed. All neuroblastoma cells engrafted in the SCID mouse, but primary tumor growth and metastatic potential varied considerably. Expression of CD44 was associated with a metastatic pattern of the neuroblastoma cell lines. CD44-positive neuroblastomas produced multicellular metastases predominantly located in the intra- and periarterial space of the lung. CD44-negative neuroblastomas developed numerous micrometastases in the lung interstitium. In conclusion, the entire spectrum of metastatic patterns can be modeled in SCID mice using the human neuroblastoma cell lines employed in this study. Our xenograft model provides a platform for investigating the complex processes involved in metastasis formation and for testing new anti-metastatic drugs. In particular, the role of CD44 in the formation of metastasis can be evaluated.
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PMID:Expression of CD44 is associated with a metastatic pattern of human neuroblastoma cells in a SCID mouse xenograft model. 1861 20

The objective of this study was to evaluate the potential of P(0) protein, a cell adhesion molecule from peripheral nerve myelin, as a targeting ligand for liposomes. To evaluate binding characteristics and identify possible binding domains, cell-interaction studies were carried out with P(0) protein reconstituted into liposomes (P(0) liposomes) under various conditions. P(0) liposomes with intact P(0) protein were tested after endoglycosidase F treatment (cleaves the carbohydrate moiety) or trypsin digestion (removes the hydrophobic portion, residues 1-79, leaving the carbohydrate portion intact). The cellular uptake was quantitated using radioactive lipids in the liposome bilayer and a liposome-entrapped water soluble compound (inulin). The presence of intact P(0) protein in the liposome bilayer increased the rate of interaction of liposomes 3-4 times with M21 melanoma and HTB-11 neuroblastoma cells (cells of neuroectodermal origin), two times with Caki-1 renal carcinoma cells, and marginally with 3T3 fibroblasts (mesodermal origin). This binding was inhibited by anti-chick P(0) antibodies and Fab fragments. A control transmembrane glycoprotein, glycophorin A., when reconstituted in liposomes had no effect on the binding of liposomes with M21 cells. The results indicate that P(0) protein plays a specific role in the binding of liposomes to cells. Removal of the N-asparagine linked carbohydrate from the P(0) protein in the liposomes resulted in an increase of their association with M21 cells five times that of control liposomes (no protein) and two times that of the non-endoglycosidase F-treated P(0) liposomes. To further characterize the binding domains of P(0) reconstituted into liposomes, competition studies were carried out in the presence of synthetic P(0)-peptides. The competition studies indicated that both the extracellular (residues 90-96) and intracellular (residues 201-207) domain of P(0) protein may be involved in the interaction with cell membranes. The results suggest that P(0) protein is capable of mediating specific heterophilic interactions with various cell lines and targeting to cells of neuroectodermal origin may be achieved.
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PMID:Targeting liposomes through immunoglobulin superfamily domains: P0 protein as a model. 1956 84


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