Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like growth factor (IGF)-II and IGF-binding protein (IGFBP)-1.
Trophoblast growth and invasion of the uterus are tightly regulated by locally produced factors. Since insulin-like growth factor (IGF)-II is produced by the invasive human extravillous trophoblast (EVT) cells and IGF-binding protein (IGFBP)-1 by the decidual cells in situ that are in proximity to each other, we examined the possible influence of these molecules on proliferation, migration, and invasiveness of first-trimester EVT cells in culture. These EVT cell functions were respectively measured by 3H-TdR uptake, in vitro migration, and invasion assays. Secretion of invasion-associated enzymes was assessed by zymography, and IGF-binding moieties on the EVT cell were examined by affinity cross-linking. Proliferation of serum-starved EVT cells was stimulated by addition of serum but unaffected by a wide range of IGF-I, IGF-II, and IGFBP-1 concentrations. IGF-II and IGFBP-1 or their combination stimulated EVT cell invasiveness and migration, when assays were conducted in serum-reduced media. Affinity cross-linking studies failed to detect the type 1 IGF receptor, although several IGF-II-specific and IGF-II-preferring binding molecules including type 2 IGF receptor were identified on the EVT cell surface. IGF-II enhancement of invasion was unaffected in the presence of IGF-1 receptor-blocking antibody and IGF-1 failed to influence EVT cell invasion, indicating that type 1 IGF receptor was not responsible for the IGF-II effects. Secretion of gelatinases or plasminogen activators was unaltered by IGF-II or IGFBP-1. We conclude that trophoblast-derived IGF-II and decidua-derived IGFBP-1 provide autocrine/paracrine enhancement of trophoblast invasiveness largely by stimulating migration, an essential step in invasion.
Hamilton
G S
GS
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Lysiak
J J
JJ
Han
V K
VK
Lala
P K
PK
D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects; D010960:Plasminogen Activators / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011509:Proteoglycans / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000276:immunology; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors / Q000276:immunology; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*
D000906:Antibodies; D004338:Drug Combinations; D018970:Insulin-Like Growth Factor Binding Protein 1; D007797:Laminin; D011509:Proteoglycans; D017469:Receptors, Fibronectin; C059485:matrigel; D007335:Insulin-Like Growth Factor II; D003094:Collagen; D017526:Receptor, IGF Type 1; D010960:Plasminogen Activators; D018093:Gelatinases