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Expression and function of the complement membrane attack complex inhibitor protectin (CD59) in human prostate cancer
Author(s) -
Jarvis Gary A.,
Li Jing,
Hakulinen Juha,
Brady Katharine A.,
Nordling Stig,
Dahiya Rajvir,
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(19970611)71:6<1049::aid-ijc22>3.0.co;2-7
Subject(s) - du145 , cd59 , complement membrane attack complex , biology , cancer research , prostate cancer , prostate , microbiology and biotechnology , cell culture , monoclonal antibody , complement system , lncap , antibody , immunology , cancer , genetics
Protectin (CD59) inhibits homologous complement‐mediated cytolysis by preventing formation of the membrane attack complex at the point of insertion and polymerization of C9 into cell membranes. The present study investigated the expression and function of CD59 on human prostatic tumor cells in situ and on 5 human prostate cell lines in vitro originating from either metastatic tumors or benign prostate hypertrophy epithelial cells. Immunohistochemical staining of prostate carcinoma tissue with monoclonal antibody (MAb) MEM43 revealed weak to moderately strong expression of CD59 by prostate glandular epithelial cells. Flow cytometry with MEM43 demonstrated that the 5 prostate cell lines expressed different relative quantities of CD59. Indirect immunofluorescence analysis revealed uniform membrane staining of DU145 and PC3 cell lines with no membranous granularity in the staining pattern. Western immunoblots with MAb BRIC 229 showed that PC3 and DU145 cells express CD59 with a m.w. of 18‐25 kDa. Treatment of DU145 and PC3 cells with phosphatidylinositol‐specific phospholipase C caused a significant decrease of CD59 expression indicating that the CD59 expressed by prostate cancer cells is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) linkage. PC3 and DU145 cells were completely resistant to human complement‐mediated cytolysis but became sensitive to killing in the presence of the CD59‐neutralizing MAb YTH53.1. We conclude that malignant and benign human prostate cells express CD59 that is GPI‐linked to the cell surface and that CD59 may regulate the immunological response to cancerous prostate cells by protecting the cells from the cytolytic activity of complement. Int. J. Cancer 71: 1049‐1055, 1997.© 1997 Wiley‐Liss Inc.