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

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 5U/ml of phosphatidylinositol-specific phospholipase C completely abolished cell-surface expression of CD59. Interferon-gamma and/or tumor necrosis factor-alpha 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. I did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine-activated killer (LAK) cells. In contrast, the whole Ig molecule of MAb HI9 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.

• Authors: L I Brasoveanu, M Altomonte, A Gloghini, E Fonsatti, S Coral, A Gasparollo, R Montagner, I Cattarossi, C Simonelli, A Cattelan
• Journal: International journal of cancer (Int J Cancer) Vol. 61 Issue 4 Pg. 548-56 (May 16 1995) ISSN: 0020-7136 [Print] United States
• PMID: 7538980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• CD59 Antigens
• Complement Inactivator Proteins
• Cytokines
• Immunoglobulin Fragments
• Membrane Glycoproteins
• RNA, Messenger
• Phosphoric Diester Hydrolases
• Phosphoinositide Phospholipase C
• Phosphatidylinositol Diacylglycerol-Lyase
• Tetradecanoylphorbol Acetate

Topics

• Antibodies, Monoclonal (pharmacology)
• Antibody-Dependent Cell Cytotoxicity (drug effects)
• Antigens, CD (analysis, immunology)
• CD59 Antigens
• Complement Inactivator Proteins (analysis, immunology)
• Cytokines (pharmacology)
• Cytotoxicity, Immunologic (immunology)
• Fluorescent Antibody Technique
• Humans
• Immunization
• Immunoglobulin Fragments (pharmacology)
• Immunohistochemistry
• Killer Cells, Lymphokine-Activated (immunology)
• Killer Cells, Natural (immunology)
• Melanoma (chemistry, immunology, secondary)
• Membrane Glycoproteins (analysis, immunology)
• Phosphatidylinositol Diacylglycerol-Lyase
• Phosphoinositide Phospholipase C
• Phosphoric Diester Hydrolases (pharmacology)
• RNA, Messenger (analysis)
• Tetradecanoylphorbol Acetate (pharmacology)