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 uterine epithelium during embryo implantation and nidation in hemochorial placental mammals is poorly understood. While limited trophoblast invasion is essential for the establishment of normal pregnancy, dysregulation of this process may contribute to the pathogenesis of choriocarcinoma, 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 endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro. Here, we report that recombinant human UG (hUG) dramatically suppresses invasion of human trophoblasts and NIH 3T3 cells through an artificial basement membrane (Matrigel) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular weight (approximately 190 kDa), nonglycosylated hUG-binding protein, readily detectable on human trophoblasts and NIH 3T3 cells but totally lacking on choriocarcinoma cells. Taken together, these results raise the possibility that (i) hUG plays a critical role in regulating cellular invasiveness, at least in part, via its previously unrecognized cell surface binding site, and (ii) some of the numerous biological activities of proteins of the UG family, reported so far, may be mediated via this binding site.
Kundu
G C
GC
Human Genetics Branch, National Insitutue of Child Health and Human Development, NIH, Bethesda, MD 20892-1830, USA.
Mantile
G
G
Miele
L
L
Cordella-Miele
E
E
Mukherjee
A B
AB
D016475:3T3 Cells; D000256:Adenoviridae; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002678:Chimera; D002822:Choriocarcinoma; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D010920:Placenta / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013539:Simian virus 40; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms; D014598:Uteroglobin / Q000494:pharmacology*; D014599:Uterus / Q000502:physiology
D002352:Carrier Proteins; D011994:Recombinant Proteins; D014598:Uteroglobin