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Complement‐regulatory proteins in ovarian malignancies
Author(s) -
Bjørge Line,
Hakulinen Juha,
Wahlström Torsten,
Matre Roald,
Meri Seppo
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970106)70:1<14::aid-ijc3>3.0.co;2-9
Subject(s) - cd59 , decay accelerating factor , cell culture , biology , ovarian cancer , cancer research , cd46 , chinese hamster ovary cell , microbiology and biotechnology , complement system , immune system , immunology , cancer , genetics
Ovarian cancer has features that makes it well‐suited for MAb adjuvant immunotherapy. Several of the MAbs used in clinical trials mediate cancer 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 factor (DAF; CD55) was more heterogeneously expressed, and only 75% of the tumors exhibited a moderate amount of DAF in the tumor cells. In adenoma cells, CD59 and DAF were preferentially located apically, while in adenocarcinoma cells they were expressed also at the basolateral cell surface. The ovarian‐carcinoma cell lines SK‐OV‐3, Caov‐3, SW626 and PA‐1 expressed both the 58‐and the 68‐kDa isoforms of MCP. DAF was present as a glycosyl‐phosphatidylinositol(GP1)‐anchored 70‐kDa glycoprotein. The surface‐expression level of DAF varied, and correlated with the vulnerability of the cells to C‐mediated lysis. CD59 was expressed as a GPl‐linked 19‐to 25‐kDa protein exhibiting multiple glycosylation variants. The surface expression of CD59 correlated with the amount of the main 1.9 + 2.1‐kb CD59 mRNA transcripts. Neutralization of CD59 with an anti‐CD59 MAb significantly enhanced C‐mediated killing of the cell lines. Low expression of C regulators on the PA‐1 teratocarcinoma cell line was associated with high sensitivity to C lysis. Thus, the expression of C regulators on malignant ovarian cells may constitute a tumor escape mechanism, and is a critical parameter to be examined when MAb therapy is being considered. © 1997 Wiley‐Liss, Inc.