HCG increases trophoblast migration in vitro via the insulin-like growth factor-II/mannose-6 phosphate receptor.
We have previously shown that both HCG and insulin-like growth factor-II (IGF-II) stimulate trophoblastic invasion. Furthermore, the invasion-promoting function of IGF-II resulted from IGF-II mannose 6-phosphate receptor (IGF-II/M6PR) activation. Since HCG and IGF-II did not have an additive effect on cell migration of extravillous trophoblast (EVT) cell line, HTR-8 SVneo, we hypothesized that HCG actions are mediated via alterations in the expression and/or function of IGF-II axis. HCG treatment (50-50,000 mU/ml) of the HTR-8/SVneo cells did not alter the expression of either insulin-like growth factor-I or IGF-II mRNA or peptide synthesis, but caused (i) an increase in the (125)I-IGF-II binding to EVT cells, and (ii) an increase in the externalization rate of the IGF-II binding sites without affecting their internalization. This effect was due to the increase in the number of IGF-II binding sites in the plasma membrane without any change in the IGF-II binding affinity. Although HCG did not influence the abundance of IGF-II/M6PR mRNA or protein, anti-IGF-II/M6PR antibody decreased HCG-induced migration of EVT, supporting the hypothesis that HCG might stimulate EVT migration by increasing IGF-II binding to the plasma membrane and subsequently by increasing the IGF-II effect probably mediated via the IGF-II/M6PR.
Zygmunt
M
M
MRC Group in Fetal and Neonatal Health and Development, The Lawson Research Institute and The Child Health Research Institute, London, Ontario, Canada. marek.t.zygmunt@gyn.med.uni-giessen.de
McKinnon
T
T
Herr
F
F
Lala
P K
PK
Han
V K M
VK
D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000276:immunology / Q000378:metabolism*; D014327:Trophoblasts / Q000502:physiology*
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II