Activator Protein-2 Impairs the Invasion of a Human Extravillous Trophoblast Cell Line

The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) α and AP-2γ act as suppressors of tumor invasion. The present study examined the expressions of AP-2α and AP-2γ in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2α and AP-2γ were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2α or AP-2γ into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2α or AP-2γ decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2α and AP-2γ were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-α, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-α, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.