Membrane-bound regulators of complement activation in uveal melanomas. CD46, CD55, and CD59 in uveal melanomas.
OBJECTIVE
To identify the presence of membrane-bound regulators of complement activation (m-RCA) on uveal melanomas and uveal melanoma cell lines and to examine their role in the inhibition of complement-mediated lysis in vitro.


METHODS
Immunohistochemistry and flow cytometric analysis with monoclonal antibodies directed against m-RCA CD46, CD55, and CD59 were applied to tissue sections of 10 uveal melanomas, three primary uveal melanoma cell lines, and one uveal melanoma metastatic cell line. A microcytotoxicity test was used for measuring antibody-dependent complement-mediated lysis.


RESULTS
The tissue sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59. Complement-mediated lysis in the presence of human complement was increased after partial removal of the m-RCA CD55 and CD59 with phosphatidylinositol-specific phospholipase C from the uveal melanoma cell line 92-1.


CONCLUSIONS
These results demonstrate that CD46, CD55, and CD59 are expressed in uveal melanomas and that CD55 or CD59, or both, plays a role in resistance to complement-mediated cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have implications for the effectiveness of the anti-tumor response and in the therapeutic application of monoclonal antibodies directed against tumor-associated antigens.
Goslings
W R
WR
Department of Ophthalmology, Leiden University Hospital, Netherlands.
Blom
D J
DJ
de Waard-Siebinga
I
I
van Beelen
E
E
Claas
F H
FH
Jager
M J
MJ
Gorter
A
A
D000368:Aged; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000032:analysis*; D018958:CD55 Antigens / Q000032:analysis*; D018957:CD59 Antigens / Q000032:analysis*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000473:pathology; D002830:Choroid Neoplasms / Q000276:immunology / Q000473:pathology; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D014604:Uveal Neoplasms / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D015395:Histocompatibility Antigens Class I; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins