| 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 neuroblas, toma 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. |
| Keywords: |
human cell; flow cytometry; antigen expression; phenotype; cell differentiation; tumor cells, cultured; carcinogenesis; cell type; cell transformation, neoplastic; monoclonal antibody; molecular cloning; blotting, western; membrane antigen; neuroblastoma; membrane glycoproteins; cytotoxicity, immunologic; antigens, cd; clone cells; complement; membrane cofactor protein; cytotoxicity tests, immunologic; antibodies, blocking; cd59 antigen; antigens, cd59; complement system proteins; humans; human; priority journal; article; antigens, cd46; antigens, cd55; complement inactivator proteins
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