Human Chorionic Gonadotropin (hCG) as Inhibitior of E-selectin-mediated Cell Adhesion

Abstract

Objective: Human chorionic gonadotropin (hCG) is a placental glycoprotein hormone of clinical importance. It is secreted into maternal circulation, amniotic fluid, urine and is also found in the serum and urine of patients with malignant trophoblastic diseases. Depending on the source, we detected a remarkable expression of sialyl Lewis^x on this protein. Sialyl Lewis^x is known as a minimal ligand recognized by selectins, which are involved in cell adhesion processes in inflammatory and metastatic diseases. In this context, the purpose of the study was to explore the ability of hCG to serve as a selectin antagonist. Materials and Methods: We purified hCG from human amniotic fluid, serum and urine of pregnant women and from supernatants of the trophoblastic tumour cell lines Jeg3 and BeWo by immunoadsorption chromatography. The proteins were functionally tested for a specific blockade of the E-selectin-mediated cell adhesion in vitro. The efficiencies of hCG from different origins were compared. Results: We found that hCG isolated from serum, amniotic fluid and supernatant of the cell line Jeg3 were strong inhibitors with at least 10³-fold higher potency compared to the monovalent tetrasaccharide sialyl Lewis^x. As expected from the carbohydrate expression, hCG isolated from the urine of pregnant women, but even from the supernatant of BeWo cells, showed no inhibitory effect. Conclusion: hCG is an effective selectin antagonist. This fact suggests that hCG may play a role in preventing leukocyte adhesion on the foetal syncytiotrophoblast or the metastatic activity of trophoblastic tumour cells.