title: Schwannian cell differentiation of human neuroblastoma cell lines in vitro induced by bromodeoxyuridine.
abstract: In normal development the neural crest gives rise to sympathetic neuroblasts, sensory and autonomic ganglia, as well as Schwann cells. One tumor arising from this tissue is the neuroblastoma (NB), a malignancy of the adrenergic component of the sympathetic nervous system. Recent histological studies have shown that neuroblastomas can present with a schwannian cell component, rich in S100 protein. We have investigated the differentiation of NB cell lines, GOTO and RT-LN-1, into a schwannian cell phenotype using bromodeoxyuridine (BrdU). This agent induced morphological changes in these cell lines. Flat-epithelial cells were identified in the GOTO cell line and both flat-epithelial and neuronal phenotypes were found in the RT-LN-1 cell line. S100 protein (beta-Subunit) was induced in both cell lines after 18-25 days of BrdU treatment as determined by enzyme-linked immunoassay. In addition increase in the beta-subunit of S100 protein was identified in BrdU-treated flat-epithelial cells by indirect immunofluorescence using a monoclonal antibody specific for the beta-subunit of the protein. Cyclic nucleotide phosphodiesterase activity significantly increased in both BrdU-treated NB cell lines, as compared with nontreated cells. However no significant increase of glial fibrillary acidic protein in BrdU-treated cells was found either by enzyme-linked immunoassay or indirect immunofluorescence using a monoclonal antibody to glial fibrillary acidic protein. Thus, cells with Schwann cell characteristics can clearly be identified in the neuroblastoma cell lines after BrdU treatment. Fluorescence-activated cell sorting analysis revealed no quantitative changes in cell membrane antigens recognized by monoclonal antibodies UJ-13A (neuroectodermal associated antigen) and anti-Thy-1 (Thy-1) on BrdU treatment. In contrast, UJ-127-11 (neuroectodermal associated) decreased, and W6/32 and BB7.7 (HLA-ABC) and BBM.1 (beta 2-microglobulin) markedly increased in both BrdU-treated cell lines. No induction of L243 (HLA-DR), B7/21 (HLA-DP), and Genox 3.55 (HLA-DQ) was noted. The increased HLA-ABC (HLA class I) antigen may enable BrdU-treated NB cells to be recognized by cytotoxic T-cells. This may be related to the pathological evidence that NB patients whose tumors are rich in S100 protein have a better prognosis. Further studies on the potential of differentiation agents to induce a phenotypic change, that is associated with an improved prognosis for NB patients, are required.
authors.affiliation: Children's Research Hospital, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Sawada
authors.forename: Y
authors.initials: Y
authors.lastname: Horii
authors.forename: J T
authors.initials: JT
authors.lastname: Kemshead
authors.forename: T
authors.initials: T
authors.lastname: Hino
authors.forename: H
authors.initials: H
authors.lastname: Morioka
authors.forename: H
authors.initials: H
authors.lastname: Hosoi
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007382:Intermediate Filaments / Q000276:immunology; D009447:Neuroblastoma / Q000032:analysis / Q000473:pathology*; D009418:S100 Proteins / Q000032:analysis; D012583:Schwann Cells / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000954:Antigens, Surface; D005904:Glial Fibrillary Acidic Protein; D009418:S100 Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D001973:Bromodeoxyuridine