Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide

1 The expression of hepatocyte growth factor (HGF) is essential for normal placental development although its function is unknown. In this study we ex amined the effect of HGF on trophoblast cell motility and invasion of fibri n gels and investigated the possible role of nitric oxide (NO) in this proc ess. 2 The human extravillous trophoblast cell line SGHPL-4 express both the con stitutive and inducible isoforms of nitric oxide synthase (NOS). 3 HGF significantly stimulates cell motility in monolayer culture, the inva sion of fibrin gels and the production of guanosine 3':5'-cyclic monophosph ate (cyclic GMP). 4 Invasion, motility and cyclic GMP production were inhibited by N-g-monome thyl-L-arginine (L-NMMA). 5 Cell motility was also significantly inhibited by the inducible NOS speci fic inhibitor 1400 W. 6 Neither 8 Br-cyclic GMP nor the NO donor spermine-NO had any significant effect on basal trophoblast cell motility. 7 The data presented in this stu dy demonstrate a direct effect of trophoblast-derived NO synthesis on troph oblast cell function and support the idea that HGF is involved in the regul ation of trophoblast invasion through mechanisms that involve the productio n of NO. However neither exogenous NO nor activation of cyclic GMP-dependen t pathways alone are sufficient to stimulate trophoblast cell motility.