Upregulation of human cytotrophoblast invasion by hepatocyte growth factor

Mesenchymal-epithelial interactions exert powerful influences on tissue arc hitecture. At the molecular level, hepatocyte growth factor (HGF; produced by mesenchyme) and its c-met tyrosine kinase receptor (expressed on epithel ial cells) participate in this paracrine dialogue. Zn the present study, an ti-HGF immunoreactivity was usually detected in association with the mesenc hymal cores of chorionic villi in situ, whereas cytotrophoblasts (CTBs) sta ined for c-met. Ln pre-eclampsia, mesenchymal HGF staining was either very low or was not observed, whereas CTB c-met expression was unchanged compare d with control samples. These findings suggest that faulty signals emanatin g from the villus mesenchyme may contribute to the failure of CTB invasion that is associated with pre-eclampsia. In the present study, this hypothesi s was tested and it was found that HGF treatment stimulates CTB invasion in vitro by four times. These immunolocalization and functional data indicate that HGF-c-met interactions play a key role in regulating the depth of CTB invasion in normal pregnancy and preeclampsia.