RECOMBINANT HUMAN UTEROGLOBIN SUPPRESSES CELLULAR INVASIVENESS VIA A NOVEL CLASS OF HIGH-AFFINITY CELL-SURFACE BINDING-SITE

The mechanism(s) that regulates invasion of trophoblasts through the u terine epithelium during embryo implantation and nidation in hemochori al placental mammals is poorly understood. While limited trophoblast i nvasion is essential for the establishment of normal pregnancy, dysreg ulation of this process may contribute to the pathogenesis of chorioca rcinoma, a highly invasive and lethal form of cancer arising from the trophoblasts. We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endom etrial epithelium during pregnancy, has a potent antichemotactic effec t on neutrophils and monocytes in vitro. Here, we report that recombin ant human UG (hUG) dramatically suppresses invasion of human trophobla sts and NIH 3T3 cells through an artificial basement membrane (Matrige l) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular we ight (approximate to 190 kDa), nonglycosylated hUG-binding protein, re adily detectable on human trophoblasts and NIH 3T3 cells but totally l acking on choriocarcinoma cells. Taken together, these results raise t he possibility that (i) hUG plays a critical role in regulating cellul ar invasiveness, at least in part, via its previously unrecognized cel l surface binding site, and (ii) some of the numerous biological activ ities of proteins of the UG family, reported so far, may be mediated v ia this binding site.