Transforming growth factor-beta1 regulates hepatocyte growth factor-induced trophoblast motility and invasion.
During placental development extravillous trophoblasts invade the uterine wall in a tightly regulated manner dependent on both pro- and anti-invasive molecules. We have shown using the extravillous trophoblast cell line, SGHPL-4, that both cellular invasion and motility are stimulated by hepatocyte growth factor (HGF). It has previously been demonstrated that transforming growth factor=beta1 (TGF-beta1), produced by the decidua, inhibits extravillous trophoblast proliferation and invasion. It was the aim of this study to determine whether TGF-beta1 could modulate HGF-induced motility and invasion and, if so, examine the mechanism involved. TGF-beta1 significantly inhibited the growth of SGHPL-4 cells stimulated with 10 per cent serum. HGF-stimulated trophoblast cell invasion and motility were significantly inhibited by TGF-beta1. Neither HGF nor TGF-beta1 had an effect on SGHPL-4 cell growth under the conditions used for the invasion and motility experiments (0.5 per cent serum). Previous studies suggest that both HGF-stimulated trophoblast invasion and motility may be regulated by the production of nitric oxide. TGF-beta1 was found to significantly decrease HGF-induced iNOS expression therefore suggesting a novel mechanism by which TGF-beta1 could regulate motility and invasion.
Tse
W K
WK
Department of Biochemistry and Immunology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK.
Whitley
G St J
GS
Cartwright
J E
JE
D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D003470:Culture Media; D005260:Female; D005312:Fetal Blood; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
D003470:Culture Media; D011993:Recombinant Fusion Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D008156:Luciferases; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II