Expression of protectin (CD59) in human melanoma and its functional role in cell‐ and complement‐mediated cytotoxicity

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Abstract
Immunohistochemical and/or indirect immunofluorescence analysis with monoclonal antibody (MAb) H19 demonstrated the expression of protectin (CD59) in 54 surgically removed metastatic melanoma lesions and on 8 out of 12 melanoma cell lines. CD59 expression had a low degree of intra‐ and intertumor heterogeneity. SDS‐PAGE analysis showed that the molecular weight of CD59 expressed on melanoma cells is about 20 kDa. Treatment of melanoma cells with 5 U/ml of phosphatidylinositol‐specific phospholipase C completely abolished cell‐surface expression of CD59. Interferon‐γ and/or tumor necrosis factor‐α or phorbol 12‐myristate 13‐acetate neither modulated the expression of CD59 by melanoma cells nor influenced the amounts of CD59‐specific mRNA. F(ab')2 fragments of anti‐CD59 MAb YTH53.1 did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine‐activated killer (LAK) cells. In contrast, the whole lg molecule of MAb H19 or YTH53. I significantly (p < 0.05) enhanced NK‐cell‐mediated lysis of melanoma cells, suggesting the induction of antibody‐dependent cell‐mediated cytotoxicity. Lastly, masking of CD59 by MAb YTH53. I or its F(ab')2 fragments significantly (p < 0.05) enhanced, in a dose‐dependent fashion, the lysis of anti‐GD3‐sensitized melanoma cells by homologous complement. These data demonstrate that CD59 expressed by human melanoma cells might regulate host‐tumor interaction by protecting neoplastic cells from complement‐mediated lysis. © 1995 Wiley‐Liss, Inc.