Upregulation of human cytotrophoblast invasion by hepatocyte growth factor.
Mesenchymal-epithelial interactions exert powerful influences on tissue architecture. At the molecular level, hepatocyte growth factor (HGF; produced by mesenchyme) and its c-met tyrosine kinase receptor (expressed on epithelial cells) participate in this paracrine dialogue. In the present study, anti-HGF immunoreactivity was usually detected in association with the mesenchymal cores of chorionic villi in situ, whereas cytotrophoblasts (CTBs) stained for c-met. In pre-eclampsia, mesenchymal HGF staining was either very low or was not observed, whereas CTB c-met expression was unchanged compared with control samples. These findings suggest that faulty signals emanating from the villus mesenchyme may contribute to the failure of CTB invasion that is associated with pre-eclampsia. In the present study, this hypothesis 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 pre-eclampsia.
Nasu
K
K
Department of Obstetrics and Gynecology, Oita Medical University, Japan.
Zhou
Y
Y
McMaster
M T
MT
Fisher
S J
SJ
D016022:Case-Control Studies; D010064:Embryo Implantation / Q000187:drug effects*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D008648:Mesoderm / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000378:metabolism*; D014327:Trophoblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met