Mechanisms of placental invasion of the uterus and their control.
Trophoblast cells of the placenta in many species have acquired mechanisms to invade the uterus, inclusive of its blood vessels, to establish efficient fetomaternal exchange of molecules. This invasion is strictly controlled both spatially and temporally and, in humans, usually continues until midgestation. Key mechanisms underlying various steps in trophoblast invasion are: (i) the attachment to the basement membrane, most likely by binding to laminin; (ii) the detachment from the basement membrane matrix, a process requiring the presence of complex-type oligosaccharides on the cell surface; and (iii) the breakdown of basement membrane components, mediated by secretion of metalloproteases (such as type IV collagenases) and serine proteases (plasminogen activator). Activation of trophoblast-derived metalloproteases appears to be plasmin dependent. Trophoblast invasiveness in situ is controlled by the microenvironment, owing to local production of anti-invasive factors by the decidual tissue of the uterus. One of these factors is TIMP (tissue inhibitor of metalloproteases), which neutralizes metalloproteases in an equimolar ratio. Another is TGF-beta (transforming growth factor-beta), which has a dual effect: it induces TIMP-1 secretion by the trophoblast and decidual cells and promotes differentiation of invasive trophoblast cells into multinucleated giant cells, which are presumably noninvasive. Thus, TGF-beta provides the key control of trophoblast invasiveness in situ. This control is lost in certain choriocarcinomas. In contrast to the response shown by the normal trophoblast, JAR and JEG-3 choriocarcinoma cell invasiveness does not seem to be inhibited by TGF-beta. In fact, in preliminary studies, JAR cells responded to TGF-beta by increased invasiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
Graham
C H
CH
Department of Anatomy, University of Western Ontario, London, Canada.
Lala
P K
PK
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002822:Choriocarcinoma / Q000473:pathology; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D010929:Placentation; D011247:Pregnancy; D014327:Trophoblasts / Q000502:physiology*; D014594:Uterine Neoplasms / Q000473:pathology; D014599:Uterus / Q000166:cytology*