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

We have investigated the effect of interferon-gamma (IFN-gamma) treatment of neuroblastoma cells on the susceptibility to lysis by lymphokine-activated killer (LAK) cells and examined the participation of cell-adhesion molecules on the target cells in LAK cell lysis. Untreated neuroblastoma cells expressed lymphocyte-function-associated antigen 3 (LFA-3) and neural-cell-adhesion molecule (NCAM), but did not express MHC-class-I, MHC-class-II, or intercellular-adhesion molecule I (ICAM-I). IFN-gamma treatment of neuroblastoma cells induced the expression of MHC-class-I and ICAM-I antigens, but did not affect the expression of MHC-class-II, LFA-3, and NCAM. This was accompanied by an increased susceptibility to lysis by LAK cells. Anti-ICAM-I antibody inhibited partially the increased sensitivity of IFN-gamma-treated neuroblastoma cells to LAK cell lysis, and blocked completely the increase in binding of LAK cells observed after IFN-gamma treatment of the target cells. These results suggest that the increased LAK sensitivity of IFN-gamma-treated neuroblastoma cells is partially attributable to the induction of ICAM-I on neuroblastoma cells and indicate that post-binding events also play a role in the increased sensitivity to LAK cell lysis observed after IFN-gamma treatment.
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PMID:Increased susceptibility of IFN-gamma-treated neuroblastoma cells to lysis by lymphokine-activated killer cells: participation of ICAM-1 induction on target cells. 167 70

The neural cell adhesion molecule (N-CAM/CD56) is a member of the Ig supergene family that has been shown to mediate homophilic binding. Several isoforms of N-CAM have been identified that are expressed preferentially in different tissues and stages of embryonic development. To examine the primary structure of N-CAM expressed in leukocytes, N-CAM cDNA were generated by polymerase chain reaction from RNA isolated from normal human NK cells and the KG1a hematopoietic leukemia cell line. The sequence of leukocyte-derived N-CAM cDNA was essentially identical with N-CAM cDNA from human neuroblastoma cells that encode the 140-kDa isoform of N-CAM. Inasmuch as N-CAM is preferentially expressed on human NK cells and a subset of T lymphocytes that mediate MHC-unrestricted cell-mediated cytotoxicity, we examined the potential role of N-CAM in cell-mediated cytotoxicity and heterotypic lymphocyte-tumor cell adhesion. N-CAM loss mutants were established from the human N-CAM+ KG1a leukemia cell line, and N-CAM cDNA was transfected into a human colon carcinoma cell line and murine L cells. Using this panel of mutants and transfectants, it was determined that expression of N-CAM on these target cells does not affect susceptibility to resting or IL-2-activated NK cell-mediated cytotoxicity. Moreover, expression of N-CAM in these transfectants failed to induce homotypic or heterotypic cellular adhesion. Collectively, these studies indicate that homophilic N-CAM interactions probably do not mediate a major role in the cytolytic interaction between NK cells and N-CAM+ tumor cell targets.
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PMID:Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). 171 Feb 51

mAb were used in an immunocytochemical assay to examine beta 2-microglobulin (b2-m) and class I MHC expression in human neuroblastoma cell lines. In lines with weak class I expression among the whole population, under ordinary assay conditions, strong b2-m and class I expression were concentrated in a small subpopulation. In positive cells, Ag was not restricted to any part of the cell body or processes. Strong expression was not required for establishment of any morphologic form or any type of cell contact. These findings complement studies in other experimental systems, where a nonimmunologic role for class I or b2-m in neural cell growth was not revealed. When the microscopic assay was modified to reveal Ag within the internal membrane system, b2-m was detected in every neuroblastoma cell. Most often, the Ag appeared as a ring around the nucleus, or in a punctate distribution in the juxtanuclear area. Internal expression of HLA chains and class I molecules was more difficult to detect, possibly reflecting a normal excess of b2-m. These findings increase understanding of MHC regulation in neural cell lines. They provide the technical and conceptual background for examination of internal MHC Ag in neural tissue.
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PMID:MHC regulation in neural cells. Distribution of peripheral and internal beta 2-microglobulin and class I molecules in human neuroblastoma cell lines. 210 97

Cultured human neuroblastoma cells express low levels of class I (MHC) surface antigen. In order to determine if this low expression is representative of the clinical tumor, this study investigates class I expression in archival human neuroblastoma. Whereas stages I to IV neuroblastoma expressed low levels of class I antigen, stage IV-S tumor cells expressed normal levels, similar to control tissues. Expression of class I antigen in tumors from survivors of stage III neuroblastoma was significantly greater than in tumors from nonsurvivors. Tumors comprised predominantly of ganglion cells expressed significantly more class I antigen than neuroblasts. These data suggest that class I MHC expression may play a role in the natural history of human neuroblastoma.
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PMID:The relationship of class I MHC antigen expression to stage IV-S disease and survival in neuroblastoma. 232 54

Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.
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PMID:IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity. 245 35

Neural cell adhesion molecule (N-CAM) is a membrane glycoprotein expressed on neural and muscle tissues that is involved in homotypic adhesive interactions. We have demonstrated that N-CAM also is expressed on hematopoietic cells, and is recognized by the anti-Leu-19 mAb. Leu-19 is preferentially expressed on NK cells and T lymphocytes that mediate MHC-unrestricted cytotoxicity, but is also present on some myeloid leukemia cell lines. On NK cells, T cells, the KG1a.5 hematopoietic cell line, and a neuroblastoma cell line, Leu-19 is a approximately 140-kD polypeptide with N-linked carbohydrates and abundant sialic acid residues. Sequential immunoprecipitation and peptide mapping demonstrated that the Leu-19 and N-CAM molecules expressed on leukocyte and neuroblastoma cell lines are similar structures. These findings suggest that the Leu-19 antigen on leukocytes may be involved in cell adhesion, analogous to the function on N-CAM on neural cells.
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PMID:Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. 247 77

Testing with a panel of 26 monoclonal antibodies (MAbs) showed the antigenic profile of 13 human neuroblastoma cell lines to be characterized by a generally poor antigenic expression; therefore, Interferon-gamma (IFN-gamma), dibutyryl cyclic-AMP and retinoic acid were used to analyse the modulation of surface antigenic expression during differentiation. Treatment of neuroblastoma cell lines with IFN-gamma resulted mainly in induction or increase of class-I MHC antigenic expression. Induction of class-II MHC antigens was obtained on only one neuroblastoma cell line out of 13, thus representing an exceptional event. An increase in some other antigens expressed by neuroblastoma cell lines was also observed. In contrast, and in addition to morphological maturation, treatment of these cell lines with the differentiation inducer dibutyryl-cyclic-AMP (dbc-AMP), resulted in general down-modulation of antigenic expression, particularly of neuroblastoma-associated 5A7 or Leu7 antigens. Retinoic acid treatment had no significant effect on MHC antigens, but it decreased expression of 5A7 and Leu7 antigens, and markedly increased the expression of the melanoma-associated antigen Me14-D12. The similarity between the antigenic profile of in vitro differentiated neuroblastoma cells and that of mature ganglioneuroma cells suggests that compounds like cyclic-AMP or retinoic acid are excellent tools for further investigations of the mechanisms of neuroblastoma differentiation and might have important clinical applications.
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PMID:In vitro antigenic modulation of human neuroblastoma cells induced by IFN-gamma, retinoic acid and dibutyryl cyclic AMP. 303 Sep 44

Melanomas from different patients have been shown to express shared tumor antigens, which can be recognized in the context of the appropriate MHC class I molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens are expressed on other tumors of neuroectodermal origin, four melanoma-specific cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes (TIL) were tested for lysis of a panel of 23 HLA-A2+ neuroectodermal tumor cell lines of various histologies, including retinoblastoma (1), neuroblastoma (8), neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5). Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23 neuroectodermal tumor lines, and could be enhanced by treatment with interferon gamma (IFN gamma). Following IFN gamma treatment, three Ewing's sarcoma lines were lysed by at least one melanoma TIL culture, and levels of lysis were comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal antibodies directed against MHC class I molecules and against CD3, indicating specific immune recognition of tumor-associated antigens. None of the other neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non-MHC-restricted lymphokine-activated killer cells. This demonstration of immunological cross-reactivity between melanomas and Ewing's sarcomas, two tumors of distinct histological types with a common embryonic origin, has implications for the developmental nature of these CTL-defined tumor antigens. It also raises the possibility that specific antitumor immunotherapies, such as vaccines, may be reactive against more than one form of cancer.
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PMID:Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T lymphocytes: evidence for antigen sharing by tumors derived from the neural crest. 751 27

Previous work has demonstrated that unique isoforms of nonmuscle myosin heavy chain II-B (MHC-B) are expressed in chicken and human neuronal cells (Takahashi, M., Kawamoto, S., and Adelstein, R. S. (1992) J. Biol. Chem. 267, 17864-17871). These isoforms, which appear to be generated by alternative splicing of pre-mRNA, differ from the MHC-B isoform present in a large number of nonmuscle cells in that they contain inserted cassettes of amino acids near the ATP binding region and/or near the actin binding region. The insert near the ATP binding region begins after amino acid 211 and consists of either 10 or 16 amino acids. The insert near the actin binding region begins after amino acid 621 and consists of 21 amino acids. Using a variety of techniques, we have studied the distribution and expression of the inserted MHC-B isoforms. In the developing chicken brain, mRNA encoding the 10-amino acid insert gradually increases after embryonic day 4, peaks in the 10-14-day embryo, and then declines. In contrast, the mRNA encoding the 21-amino acid insert appears just before birth and is abundantly expressed in the adult chicken cerebellum. There is a marked species difference between the distribution of the inserted isoforms in adult tissues. The mRNA encoding MHC-B containing the 10-amino acid insert near the ATP binding region is expressed at low levels in the adult chicken brain, but makes up most of the MHC-B mRNA expressed in the human cerebrum and approximately 90% of MHC-B in the human retina. It is also expressed in neuronal cell lines. The mRNA encoding MHC-B containing the 21-amino acid insert is abundantly expressed in the chicken cerebellum and human cerebrum, but is absent from the retina and cell lines. Employing human retinoblastoma (Y-79) and neuroblastoma (SK-N-SH) cell lines, an increase in expression of mRNA encoding the 10-amino acid inserted isoform was seen following treatment by a number of agonists or by serum deprivation. In each case, expression of the inserted MHC-B isoform correlated with cell differentiation (neuronal phenotype) and inhibition of cell division. Using a rat pheochromocytoma cell line (PC12), we found that prior to treatment with nerve growth factor (NGF), there was no evidence for either inserted isoform, although noninserted MHC-B was present. NGF treatment resulted in the appearance of mRNA encoding MHC-B containing the 10-amino acid insert, concomitant with neurite outgrowth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuronal cell expression of inserted isoforms of vertebrate nonmuscle myosin heavy chain II-B. 778 16

Recombinant gamma-interferon (IFN-gamma) has recently been shown to be one of the most effective inducers of neuroblastoma (NB) cell differentiation. Since increasing evidence indicates that expression of MHC class-I and class-II antigens by tumour cells is important for immunorecognition and cell targeting, we tested whether induction of NB cell differentiation by IFN-gamma is followed by expression of HLA class-I and class-II molecules. LAN-5 human NB cell line completely lacks HLA class-I antigens. Their expression was induced in a dose-dependent manner by IFN-gamma. HLA class-II molecules are also absent on LAN-5 cells, but only DP antigens were dose-dependently induced by IFN-gamma, while DR and DQ molecules were unaffected by the treatment. To confirm and extend the immunological data to all the class-II molecules, we performed Northern blot analysis, observing that DP alpha mRNA was induced in a dose- and time-dependent manner. DO beta and DZ alpha genes were also induced peaking after 3 days of IFN-gamma treatment. DR beta and DQ beta genes, which were not induced by IFN-gamma, gave a normal pattern of enzyme restriction by Southern blot. To get an insight into the regulation of HLA class-II gene expression in the neuronal model, we measured the decline of the steady-state HLA class-II mRNA. DO beta mRNA rapidly returned to baseline level after removing IFN-gamma, while the decay rates of DP alpha and DZ alpha mRNA were very slow. This might indicate different regulation at the post-transcriptional level for DO beta mRNA with respect to DP alpha and DZ alpha mRNA. To strengthen these findings we evaluated the half-lives of the mRNA after IFN-gamma induction by means of actinomycin D treatment. HLA-DO beta mRNA had a shorter half-life, while DZ alpha and DP alpha had a longer decay rate. Finally, we report that treatment of LAN-5 cells with cycloheximide did not alter the rate of transcription of the HLA-DP alpha gene, suggesting that no protein factor(s) is/are needed to maintain DP alpha gene expression.
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PMID:Uncoordinate induction and differential regulation of HLA class-I and class-II expression by gamma-interferon in differentiating human neuroblastoma cells. 824 79


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