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

Human nerve growth factor (NGF) receptor (NGFR) cDNA was transfected into a neuroblastoma cell line (HTLA 230) which does not express a functional NGF-NGFR signal transduction cascade. Short-term treatment of stably transfected cells (98-3) expressing membrane-bound NGF receptor molecules resulted in a cell cycle-dependent, transient expression of the c-fos gene upon treatment with NGF, suggesting the presence of functional high-affinity NGFR. Extensive outgrowth of neurites and cessation of DNA synthesis occurred in transfectants grown on an extracellular matrix after long-term treatment with NGF, suggesting terminal differentiation. Our data support the idea that introduction of a constitutively expressed NGFR cDNA into cells with neuronal background results in the assembly of a functional NGF-NGFR signal cascade in a permissive extracellular environment.
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PMID:Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA. 216 46

A continuous tumor cell line (LAP-35) was established from a primitive neuroectodermal tumor of bone from the right tibia of a 12-year-old female. The neural character of the cell line was documented by the spontaneous growth of neurites and by the presence of several neural markers, including neuron-specific enolase (NSE), S-100 protein, neurofilaments, chromogranin A, synaptophysin and positivity to monoclonal antibodies UJ127.11, UJ13A, UJ181.4. Cell-sorter analysis showed a high expression of nerve growth factor receptor (NGFr) and major histocompatibility complex class I-related molecules. A unique cytogenetic profile was observed, including a reciprocal chromosomal translocation (rct) 11:22 (q24;q12), typically associated with Ewing's sarcoma and neuroepithelioma, and deletion of the short arm of chromosome 1 (lp-), otherwise a feature of neuroblastoma. N-myc proto-oncogene was neither amplified nor expressed, whereas the expression of c-myc was documented by northern blot analysis. These features distinguish this new cell line from previously reported neuroectodermal cell lines, identifying LAP-35 as a unique model of a group of neural bone tumors that share characteristics of neuroblastoma as well as neuroepithelioma.
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PMID:Establishment and characterization of a primitive neuroectodermal tumor of bone continuous cell line (LAP-35). 217 80

Identification of growth factors and receptors in mesenchymal tumors may be crucial to understanding of growth regulation in sarcomas. During an immunohistochemical study of the expression of growth factors and receptors in human soft tissue tumors (STT), only 1 antisera capable of working in paraffin-embedded tissue was noted. A detailed study of 141 STT was undertaken to determine the frequency of expression of nerve growth factor receptor (NGF-R), its specificity and sensitivity for neural tumors, and the effect of fixation on detection. In normal mesenchymal tissue, only nerve sheath and perivascular staining was seen. No immunoreactivity was seen in many tumors including rhabdomyosarcoma, angiosarcoma, liposarcoma, Ewing's sarcoma, and alveolar soft part sarcoma. Less than 15% of tumors of smooth muscle, fibrous, or fibrohistiocytic origin showed immunoreactivity, usually focal. In contrast, a high frequency of immunoreactivity was noted in tumors of neural origin (74%). This included granular cell tumors (100%), Schwannoma/neurofibroma (91%), malignant Schwannoma (78%), neuroblastoma/neuroepithelioma (60%), and paraganglioma (57%). A high rate of reactivity was also seen in synovial sarcomas (80%), undifferentiated sarcomas (60%), and hemangiopericytomas (43%), suggesting a potential relationship to the neural phenotype. Among the neural tumors, Bouin's fixation was superior to formalin, suggesting that immunoreactivity for NGF-R is affected by fixation. This antibody may be a useful adjunct marker diagnostically.
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PMID:Expression of nerve growth factor receptor in paraffin-embedded soft tissue tumors. 245 20

A series of 22 neuroepithelioma and neuroblastoma cell lines were screened for expression of nerve growth factor receptor (NGFR) by flow cytometry, Western blotting, and Northern blotting. All 5 neuroepithelioma cell lines expressed cell surface NGFR, with 30-69% of cells NGFR positive, but the 17 neuroblastoma cell lines tested had a smaller percentage of cell surface NGFR-positive cells (0-21%) and 10 lines were completely lacking cell surface NGFR. SY5Y, a variant line with a neuronal phenotype derived from neuroblastoma line SKNSH, expressed much more NGFR than SHEP, a variant line with an epithelial-like phenotype also derived from SKNSH. By Western blotting, the Mr approximately 69,000 NGFR band was detected for all four neuroepithelioma cell lines tested but was visible for only 8 of 15 neuroblastoma cell lines tested. The band was most intense for neuroepithelioma cell lines SKNMC and TC32. For these two lines, a Mr approximately 56,000 and a Mr approximately 60,000 band were also detected. By Northern blotting, all three neuroepithelioma cell lines tested were positive for the 3.8 kilobase NGFR mRNA, but only 8 of 15 neuroblastoma cell lines were positive. Neuroepithelioma cell line TC32 and neuroblastoma cell line GICAN had the strongest expression of NGFR mRNA. These results demonstrate that NGFR is a biological marker for neuroepithelioma and that NGFR expression is heterogeneous for neuroblastoma cell lines. This series of neural cell lines differing in NGFR expression will be useful for future studies of regulation of NGFR expression and neuronal differentiation.
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PMID:Analysis of nerve growth factor receptor expression in human neuroblastoma and neuroepithelioma cell lines. 254 34

Nerve growth factor (NGF) is a protein which promotes the survival and differentiation of neuronal cells in vitro and plays an important role in neuronal development. In this study, we have examined the expression of the receptor for NGF (NGFR) in human neuronal and nonneuronal cells, both in tissue culture and in vivo. In addition to cell lines derived from neuroblastoma, astrocytoma, and melanoma, all of which share a common neuroectodermal origin, NGFR was detected in a number of cultured cells of mesenchymal, epithelial, and hematopoietic derivation. Immunohistochemical analysis showed that NGFR is expressed in several nonneural human tissues, and the cell types in which NGFR was found include derivatives from all three germ layers. Thus, our findings demonstrate that NGFR is much more widely expressed in human cells and tissues than was previously thought.
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PMID:Expression of human nerve growth factor receptor on cells derived from all three germ layers. 282 87

Nerve growth factor (NGF) is a polypeptide hormone which plays a central role in the development and growth of sympathetic and sensory neurons. The effects of NGF on target cells are mediated by a specific cell surface structure, nerve growth factor receptor (NGFr), which has been identified in human cells as a 75,000-mol-wt glycoprotein. We have used a monoclonal antibody to human NGFr to study cell-surface expression of the receptor on a panel of mouse-human neuroblastoma hybrids, and the serological typing results permit assignment of the gene coding for NGFr (NGFR) to chromosome 17q21-qter. In addition to mouse-human neuroblastoma hybrids, human NGFr was also detected on hybrids derived from fusions between mouse L-cell fibroblasts and human neuroblastoma and melanoma cells. Furthermore, induction of human NGFr expression was observed in hybrids derived from NGFr- human kidney epithelial cells and mouse L cells, but not in hybrids derived from human kidney epithelial cells and mouse RAG kidney carcinoma cells. These results suggest that cell-surface expression of human NGFr is controlled by trans-acting regulatory signals.
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PMID:Assignment of human nerve growth factor receptor gene to chromosome 17 and regulation of receptor expression in somatic cell hybrids. 302 Jul 11

The histogenesis of Ewing's sarcoma, the second most frequent primary bone tumor in humans, remains controversial. Ten Ewing cell lines were analyzed by immunological methods. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. They included ganglioside GD2, a marker of neuroectodermal tissues and tumors, and an acidic glycolipid detected by monoclonal antibody HNK-1 in the nervous system. The P61 rat monoclonal antibody that reacts with a peptide moiety of neural cell adhesion molecule (N-CAM) and a rabbit antiserum raised to purified mouse N-CAM also stained Ewing cells. Flow cytometry analysis performed using these reagents allowed the definition of four distinct Ewing phenotypes: all reagents equally stained group 1 lines; group 2 lines were strongly reactive with anti-N-CAM reagents, by contrast with a fainter staining with HNK-1 and anti-GD2 antibodies; all reagents but P61 were strongly reactive with group 3 lines; in group 4, Ewing lines were stained by P61 but only poorly by the anti-N-CAM antiserum. Several antibodies to melanoma and neuroblastoma associated antigens including two monoclonal antibodies to the nerve growth factor receptor were also found to react with Ewing cells. By contrast, all antibodies detecting antigens specifically expressed in hematopoietic cell lineages were totally unreactive. HLA class II antigens were never detected while the level of expression of class I antigens varied to a large extent. Ewing cells are characterized by a specific t(11;22)(q23-24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor. Thus, Ewing's sarcoma cells share antigenic and karyotypic features with derivatives of the neuroectoderm possibly indicating a related histogenesis.
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PMID:Neuroectoderm-associated antigens on Ewing's sarcoma cell lines. 302 14

High levels of mRNA (as assessed by northern blot) for the high-affinity nerve growth factor receptor (p140TRK) are predictive of favourable outcome in neuroblastoma. The feasibility of determining p140trk on frozen sections using a recently developed monoclonal antibody was evaluated, and immunohistochemical findings were compared to those obtained from northern blot analysis. Primary tumour samples from 28 untreated patients were quick frozen and an indirect immunofluorescence assay was performed on 4-microns acetone-fixed cryostat sections. 9 cases were positive with immunohistochemistry, and these were among the 15 cases also positive by northern blot. None of the cases negative by northern blot were positive with immunohistochemistry. The concordance rate was 79% (P < 0.03), with a sensitivity of 60% and a specificity of 100%. Immunohistochemistry can thus be rather reliable for assessing p140trk expression, even when only very small amounts of tissue are available, such as with needle biopsy.
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PMID:Immunohistochemical detection of high-affinity nerve growth factor receptor in neuroblastoma. 757 42

A gene encoding a putative third member of the insulin receptor family (called the insulin receptor-related receptor or IRR) was isolated in 1989. However, the naturally occurring protein product encoded by this gene has yet to be described. In the present studies, we have generated four monoclonal antibodies to a recombinantly expressed chimera, which contains the extracellular domain of human IRR. These antibodies were found to specifically recognize the chimeric IRR (and not the insulin or insulin-like growth factor I receptors), and two of the antibodies were capable of acting as partial agonists in the cells expressing the chimeric IRR. These antibodies have therefore been utilized to study the expression and properties of the native receptor. In contrast to the two other members of this receptor family, the endogenous IRR protein had only a very limited expression, being detected only in neuroblastomas. In primary neuroblastomas, the levels of the receptor were highest in samples from stage A tumors (those which are generally more highly differentiated and have higher levels of the nerve growth factor receptor). The endogenous IRR could also be detected in a neuroblastoma cell line (called IMR-5 cells). In these cells, IRR could be shown to be partly present as a hybrid with the insulin and insulin-like growth factor-I receptors but not with the receptor for nerve growth factor. The intrinsic tyrosine kinase activity of this endogenous IRR was activated by the agonist monoclonal antibody to IRR but not by nerve growth factor, insulin-like growth factor I, or insulin. Finally, this monoclonal antibody was found to stimulate mitogen-activated protein kinase activity in these cells. In summary, these studies demonstrate for the first time that the IRR protein is normally expressed, that its levels are highest in neuronal tissues, and that it can form hybrid receptors with the two other members of this receptor family but not with the more distantly related nerve growth factor receptor.
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PMID:Characterization of the endogenous insulin receptor-related receptor in neuroblastomas. 782 25

There has been considerable progress in the past decade in elucidating the molecular basis of malignant transformation of retinoblastoma, Wilms' tumour and neuroblastoma. For retinoblastoma, the story is relatively simple and the laboratory focus should be on rapid detection of germline mutations, identifying additional genetic changes associated with tumour progression and the prevention of second primary cancers, if possible. In the case of Wilms' tumour, the locus (or loci) responsible for hereditary predisposition is still unknown. Furthermore, the WT2 locus has not been cloned and there is no consistent evidence of oncogene activation. Clearly, there is still much to be done before we fully understand the genetic basis of this disease. Finally, substantial insights have been gained from the molecular analysis of neuroblastomas, but this tumour is perhaps the least well understood. Two sites of allelic loss have been identified (1p36 and 14q32), but the presumptive suppressor genes that are the targets of these changes have yet to be identified. Furthermore, it is not clear if either of these loci is responsible for a genetic predisposition to develop this tumour. Although N-myc amplification is a powerful prognostic marker of aggressive tumours, no other oncogene has been shown to be activated in tumours lacking amplification. Finally, the NGFR pathway may have an important role in regulating differentiation and programmed cell death in these cells, but other NGFR family pathways or unrelated genes may be involved as well. Hopefully, the next decade will provide us with answers to many of these open questions.
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PMID:Genetics of embryonal tumours of childhood: retinoblastoma, Wilms' tumour and neuroblastoma. 871 13


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