Ga. Jarvis et al., EXPRESSION AND FUNCTION OF THE COMPLEMENT MEMBRANE ATTACK COMPLEX INHIBITOR PROTECTIN (CD59) IN HUMAN PROSTATE-CANCER, International journal of cancer, 71(6), 1997, pp. 1049-1055
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.