MEMBRANE-BOUND REGULATORS OF COMPLEMENT ACTIVATION IN UVEAL MELANOMAS- CD46, CD55, AND CD59 IN UVEAL MELANOMAS

Purpose. To identify the presence of membrane-bound regulators of comp lement activation (m-RCA) on uveal melanomas and uveal melanoma cell l ines and to examine their role in the inhibition of complement-mediate d lysis in vitro. Methods. Immunohistochemistry and flow cytometric an alysis with monoclonal antibodies directed against m-RCA CD46, CD55, a nd CD59 were applied to tissue sections of IO uveal melanomas, three p rimary uveal melanoma cell lines, and one uveal melanoma metastatic ce ll line, A microcytotoxicity test was used for measuring antibody-depe ndent complement-mediated lysis. Results, The tissue sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59. Complem ent-mediated lysis in the presence of human complement was increased a fter partial removal of the m-RCA CD55 and CD59 with phosphatidylinosi tol-specific phospholipase C from the uveal melanoma cell Line 92-1. C onclusions. These results demonstrate that CD46, CD55, and CD59 are ex pressed in uveal melanomas and that CD55 or CD59, or both, plays a rol e in resistance to complement-mediated cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have implications for the e ffectiveness of the anti-tumor response and in the therapeutic applica tion of monoclonal antibodies directed against tumor-associated antige ns.