Control of Proliferation, Migration, and Invasiveness of Human Extravillous Trophoblast by Decorin, a Decidual Product1
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Notice bibliographique
Résumé
Extravillous trophoblast (EVT) cells of the human placenta progressively lose their proliferative activity in situ as EVT cell columns migrate into and invade the decidua. It remains unclear whether this is due to a terminal differentiation of EVT cells along the invasive pathway with concomitant loss of proliferative ability, or a negative regulation by decidua-derived factors, or both mechanisms. Our earlier studies provided evidence for a negative regulation by a decidua-derived factor, transforming growth factor (TGF)-beta, which inhibited proliferation, migration, and invasiveness of first-trimester EVT cells in vitro. We further discovered that decidua also produces decorin, a proteoglycan that binds TGF-beta (and in some cases, inactivates TGF-beta), which is colocalized with TGF-beta in the decidual extracellular matrix. The present study used in vitro-propagated EVT cell lines to examine whether EVT cells retain their capacity for proliferation after the process of invasion; and whether decorin exerts any effect on EVT cell proliferation, migration, or invasiveness in a TGF-beta-dependent or TGF-beta-independent manner. We also examined whether trophoblastic cancer (choriocarcinoma) JAR and JEG-3 cells responded to decorin in a similar manner. Proliferation was measured using a colorimetric (MTT) cellularity assay and immunolabeling for the Ki-67 proliferation marker. Migration and invasiveness were measured in transwells by the ability of cells to cross 8-microm pores of polycarbonate membranes in the absence or presence of an additional matrigel barrier. These experiments revealed three points. First, EVT cells retained limited but significant proliferative ability in vitro after invading matrigel. Second, that decorin alone blocked EVT cell proliferation in a dose-dependent manner. This effect remained unaffected in an additional presence of TGF-beta, which exerted antiproliferative effects on its own. The antiproliferative effect of decorin was explained by an up-regulation of the p21 protein. Third, that decorin alone or TGF-beta alone exerted antimigratory and anti-invasive effects on EVT cells, but the addition of TGF-beta to decorin did not alter decorin action. And fourth, that choriocarcinoma cells were resistant to antiproliferative, antimigratory, and anti-invasive effects of decorin. These results suggest 1) that the invasive function of EVT cells is not associated with a terminal differentiation into a noncycling state; 2) that proliferation, migration, and invasiveness of EVT cells within the decidua are independently controlled by two decidual products, TGF-beta and decorin (decorin in the decidual extracellular matrix may serve as a storage mechanism for TGF-beta in an inactive state and may be activated by EVT cell proteolytic mechanisms, thus preventing overinvasion); and 3) that choriocarcinoma cells are refractory to negative regulation by both decidua-derived factors.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle