Insulin-like growth factor binding protein-1 binds to placental cytotrophoblast alpha5beta1 integrin and inhibits cytotrophoblast invasion into decidualized endometrial stromal cultures.
Insulin-like growth factor binding protein-1 (IGFBP-1) can bind to the alpha5beta1 integrin and stimulate cellular migration in Chinese hamster ovary (CHO) cells. IGFBP-1 is a major product of the endometrium of pregnancy (decidua), and may interact with invading cytotrophoblasts expressing alpha5beta1 integrin to modulate their invasion. The present study investigated IGFBP-1 interaction with cytotrophoblast alpha5beta1 integrin, and its effects on trophoblast attachment to fibronectin and invasion into decidualized endometrial stromal cell multilayers. IGFBP-1 incubated with cytotrophoblast extracts was co-precipitated by an antibody to the alpha5 integrin subunit. Up to 55% of radiolabeled IGFBP-1 bound to cytotrophoblasts was displaced by excess non-radioactive IGFBP-1, but not by IGFBP-3. Cytotrophoblast attachment to fibronectin was inhibited by an RGD-containing octapeptide, by antibodies to the alpha5 subunit or the alpha5beta1 heterodimer, and by IGFBP-1. Cytotrophoblasts showed limited invasion into endometrial stromal multilayers decidualized in vitro secreting abundant IGFBP-1, but invaded multilayers when IGFBP-1 production was inhibited by insulin. Invasion into insulin-treated multilayers was prevented by addition of exogenous IGFBP-1 but not by IGFBP-3. These findings suggest IGFBP-1 may modulate trophoblast invasiveness.
Irwin
J C
JC
Department of Gynecology and Obstetrics, Stanford University Medical Center, CA 94305-5317, USA.
Giudice
L C
LC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001667:Binding, Competitive; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D003656:Decidua / Q000166:cytology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology; D014327:Trophoblasts / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; C047981:arginyl-glycyl-aspartic acid