EXPRESSION AND FUNCTION OF THE COMPLEMENT MEMBRANE ATTACK COMPLEX INHIBITOR PROTECTIN (CD59) IN HUMAN PROSTATE-CANCER

Protectin (CD59) inhibits homologous complement-mediated cytolysis by preventing formation of the membrane attack complex at the point of in sertion and polymerization of C9 into cell membranes. The present stud y investigated the expression and function of CD59 on human prostatic tumor cells in situ and on 5 human prostate cell lines in vitro origin ating from either metastatic tumors or benign prostate hypertrophy epi thelial cells. Immunohistochemical staining of prostate carcinoma tiss ue with monoclonal antibody (MAb) MEM43 revealed weak to moderately st rong expression of CD59 by prostate glandular epithelial cells. Flow c ytometry with MEM43 demonstrated that the 5 prostate cell lines expres sed different relative quantities of CD59. Indirect immunofluorescence analysis revealed uniform membrane staining of DU145 and PC3 cell lin es with no membranous granularity in the staining pattern. Western imm unoblots with MAb BRIC 229 showed that PC3 and DU145 cells express CD5 9 with a m.w. of 18-25 kDa. Treatment of DU145 and PC3 cells with phos phatidylinositol-specific phospholipase C caused a significant decreas e of CD59 expression indicating that the CD59 expressed by prostate ca ncer cells is anchored to the cell membrane via a glycosylphosphatidyl inositol (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 tha t malignant and benign human prostate cells express CD59 that is GPI-l inked 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. (C) 1997 Wiley-Liss, Inc.