title: Surface antigen expression and complement susceptibility of differentiated neuroblastoma clones.
abstract: Human neuroblastoma cell lines typically consist of heterogenous subpopulations of cells that are morphologically and biochemically distinct. The cell types are characterized as neuroblastic (N-type), substrate-adherent Schwann-like (S-type), or intermediate (I). These cell types can undergo spontaneous or induced transdifferentiation in vitro. We investigated the complement sensitivity of different neuroblastoma cell lines and of matched sets of cloned N- and S-type neuroblastoma cell lines. Human neuroblastoma cell lines that consisted predominantly of a neuroblastic phenotype were shown to be significantly more susceptible to human complement-mediated lysis than cell lines of other cancer types. Complement sensitivity of neuroblastoma cell lines was correlated with low levels of CD59, decay-accelerating factor, and membrane cofactor protein expression. We found that cloned S-type neuroblastoma cells were much more resistant to complement-mediated lysis than cloned N-type cells. The increased complement resistance of S-type cells was shown to be due to increased expression of membrane-bound complement inhibitors. CD59 was the single most important protein in providing S-type cells with protection from complement lysis. S-type cells were also found to express lower levels of GD2, a target antigen for a complement activating monoclonal antibody currently in clinical trials for neuroblastoma immunotherapy. The ability of S-type cells to evade complement, and the ability of S-type cells to differentiate into the more tumorigenic N-type cells, may represent a mechanism of tumor survival and regrowth, a phenomenon often observed with this cancer.
authors.affiliation: Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Caragine
authors.forename: N K
authors.initials: NK
authors.lastname: Cheung
authors.forename: S
authors.initials: S
authors.lastname: Tomlinson
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000276:immunology / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D003169:Complement Inactivator Proteins / Q000276:immunology / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D003165:Complement System Proteins