Involvement of dipeptidyl peptidase IV in extravillous trophoblast invasion and differentiation.
Previously, we reported that dipeptidyl peptidase IV (DPPIV), a membrane-bound peptidase, was expressed on human placental cytotrophoblasts. In the present study, we focused on DPPIV expression on extravillous trophoblasts (EVTs). In the first trimester, DPPIV was expressed in the proximal part of the cell column and some EVTs located in the deep portion of the decidua and myometrium. EVTs migrating in the decidua from the cell column were negative for DPPIV. In the second and third trimesters, almost all EVTs were positive for DPPIV. Because negative DPPIV expression was associated with migration or the invasive phenotype of EVTs, using JEG-3 cells (choriocarcinoma cell line) that endogenously produce DPPIV, the influence of DPPIV on the invasive activity was examined. When a competitive inhibitor of DPPIV, diprotin A, was added in Matrigel invasion assay system, JEG-3 cells exhibited a significant enhancement of invasion. Because hypoxia is reported to reduce trophoblastic invasion, the effect of hypoxia was examined on JEG-3 cells. JEG-3 cells became less invasive with increased expression of DPPIV when cultured under hypoxic conditions (1% O(2)). These results suggest that DPPIV is important for the noninvasive EVT phenotype and the down-regulation of this enzyme was strongly associated with migration or invasive EVT phenotype.
Sato
Yukiyasu
Y
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Fujiwara
Hiroshi
H
Higuchi
Toshihiro
T
Yoshioka
Shinya
S
Tatsumi
Keiji
K
Maeda
Michiyuki
M
Fujii
Shingo
S
D001483:Base Sequence; D002151:Calorimetry; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002824:Chorionic Villi / Q000201:enzymology / Q000502:physiology*; D017931:DNA Primers; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism*; D010064:Embryo Implantation / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D010920:Placenta / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D011247:Pregnancy; D017452:Receptors, IgG / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*
D017931:DNA Primers; D009842:Oligopeptides; D017452:Receptors, IgG; C041445:diprotin A; D018819:Dipeptidyl Peptidase 4