Effects of ligands or substrate of insulin-regulated aminopeptidase (IRAP) on trophoblast invasion.
Insulin-regulated aminopeptidase (IRAP) activity increases during placentation and in the invasive tumor cell of trophoblast suggesting a role for this peptidase in the invasiveness of normal and malignant trophoblast. To investigate this hypothesis, we studied the effects of substrate (OT) and inhibitors (angiotensin peptides and LVV-H7) of IRAP on the first trimester trophoblast proliferation and invasion. Addition of these peptides in the culture medium of trophoblastic cells significantly decreased metalloproteinase-9 activity and cellular invasiveness while no effect was observed on cell proliferation. The peptide IRAP inhibitors could exert their effect on cytotrophoblastic cell invasiveness by inhibition of its enzymatic activity, and thus increasing half life of the known placental peptide substrate of IRAP, OT.
Cohen
Marie
M
Department of Obstetrics and Gynaecology, Maternity, Laboratory of Hormonology, University of Geneva, Boulevard de la Cluse, Geneva 14, Switzerland. marie.cohen@hcuge.ch
Wuillemin
Christine
C
Chai
Siew Yeen
SY
Bischof
Paul
P
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D010122:Cystinyl Aminopeptidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008024:Ligands; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D013379:Substrate Specificity; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008024:Ligands; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; D020780:Matrix Metalloproteinase 9