Antiproliferative Actions of Ovine Uterine Serpin

Abstract

Ovine uterine serpin (OvUS) is a member of the serine proteinase inhibitor superfamily and is the major protein produced by luminal and glandular epithelium of the sheep endometrium during mid to late pregnancy. The protein does not have prototypical proteinase inhibitory activity but can inhibit a wide variety of lymphocyte functions such as mitogen-induced proliferation and natural killer cell cytotoxicity. The antiproliferative actions of OvUS were studied. It was demonstrated that, in addition to inhibiting lymphocyte proliferation, OvUS inhibits growth of two tumor cell lines (D17 and PC-3). The protein also interrupts development of pre-implantation embryos. Inhibition of cell proliferation is not universal, however, as OvUS did not inhibit growth of two non-tumorigenic cell lines (MDBK and BEND). The mechanism of action of inhibitory effects of OvUS is not known although experiments with inhibitors of protein kinase A indicate that the protein does not inhibit lymphocyte proliferation through this pathway. Moreover, the protein does not induce apoptosis. The finding that OvUS has antiproliferative activity is demonstrative of the wide range of functions exerted by members of the serpin superfamily. The antiproliferative property of OvUS may reflect the role of the protein during pregnancy and may be exploitable for design of new antiproliferative drugs.