COMPLEMENT-REGULATORY PROTEINS IN OVARIAN MALIGNANCIES

Ovarian cancer has features that makes it well-suited for MAb adjuvant immunotherapy. Several of the MAbs used in clinical trials mediate ca ncer cell destruction by activation of complement (C), In this study, therefore, we examined the ability of ovarian-tumor cells to resist C attack. We found that the C regulators membrane cofactor protein (MCP, CD46) and protectin (CD59) were strongly expressed in the tumor cells in all 28 benign and malignant tumors examined. Decay-accelerating fa ctor (DAF; CD55) was more heterogeneously expressed, and only 75% of t he tumors exhibited a moderate amount of DAF in the tumor cells. In ad enoma cells, CD59 and DAF were preferentially located apically, while in adenocarcinoma cells they were expressed also at the basolateral ce ll surface, The ovarian-carcinoma cell lines SK-OV-3, Caov-3, SW626 an d PA-I expressed both the 58- and the 68-kDa isoforms of MCP. DAF was present as a glycosyl-phosphatidylinositol(GP I)-anchored 70-kDa glyco protein, The surface-expression level of DAF varied, and correlated wi th the vulnerability of the cells to C-mediated lysis. CD59 was expres sed as a GPI-linked 19- to 25-kDa protein exhibiting multiple glycosyl ation variants. The surface expression of CD59 correlated with the amo unt of the main 1.9 + 2.1-kb CD59 mRNA transcripts. Neutralization of CD59 with an anti-CD59 MAb significantly enhanced C-mediated killing o f the cell lines. Low expression of C regulators on the PA-I teratocar cinoma cell line was associated with high sensitivity to C lysis. Thus , the expression of C regulators on malignant ovarian cells may consti tute a tumor escape mechanism, and is a critical parameter to be exami ned when MAb therapy is being considered. (C) 1997 Wiley-Liss, Inc.