Importance of matrix metalloproteinases in human trophoblast invasion.
Human cytotrophoblast cells are invasive by virtue of their ability to secrete metalloproteinases (MMP) capable of digesting the extracellular matrix of the endometrium. It is the aim of the present study to determine which of the known MMP is responsible for this invasive behavior and to see to what extent endometrial secretions can modulate this enzymatic activity. Under our experimental conditions, first-trimester cytotrophoblast cells invade matrigel; this invasive behavior is inhibited by phenanthroline (an inhibitor of MMP) and by a polyclonal antibody to the 92-kDa gelatinase but not to other MMP. Since cytotrophoblast cells cultured in vitro secrete the 92-kDa gelatinase, and since adhesion to a substrate increases their gelatinolytic activity, it is believed that cytotrophoblast cells invade their surrounding matrix by binding to it and by increasing their secretion of 92-kDa gelatinase which then digests the collagen type IV of their micro-environment. This process of invasion is controlled by secretions from decidual cells (but not from non-decidualized stromal cells) since conditioned medium from decidual cells inhibits the activity of the 92-kDa gelatinase released from cytotrophoblast cells.
Bischof
P
P
Department of Obstetrics and Gynecology, University of Geneva, Switzerland.
Martelli
M
M
Campana
A
A
Itoh
Y
Y
Ogata
Y
Y
Nagase
H
H
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D004717:Endometrium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007797:Laminin; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D010618:Phenanthrolines / Q000494:pharmacology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011480:Protease Inhibitors / Q000494:pharmacology; D011509:Proteoglycans; D014327:Trophoblasts / Q000502:physiology*
D000906:Antibodies; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007797:Laminin; D010618:Phenanthrolines; D011480:Protease Inhibitors; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases