Regulation of human extravillous trophoblast function by membrane-bound peptidases.
During human placentation, the invasion of extravillous trophoblasts (EVTs) into maternal decidual tissues, especially toward maternal spiral arteries, is considered an essential process for subsequent normal fetal development. However, the precise regulatory mechanisms to induce EVT invasion toward arteries and/or to protect EVTs from further invasion have not been well understood. Recently, we found that two cell surface peptidases, dipeptidyl peptidase IV (DPPIV) and carboxypeptidase-M (CP-M,) are differentially expressed on EVTs. DPPIV expression was mainly observed on EVTs that had already ceased invasion. CP-M was detected on migrating EVTs including endovascular trophoblasts in the maternal arteries. The enzymatic inhibition of these peptidases affected the invasive property of choriocarcinoma-derived cell lines, BeWo and JEG3 cells. In addition, a chemokine, RANTES, that is one of the substrates for DPPIV, enhanced invasion of EVTs isolated from primary villous explant culture and its receptor, CCR1, was specifically expressed on migrating EVTs toward maternal arteries. Furthermore, a novel membrane-bound cell surface peptidase, named laeverin, was found to be specifically expressed on EVTs that had almost ceased invasion. These findings suggest that membrane-bound peptidases are important factors regulating EVT invasion during early placentation in humans.
Fujiwara
Hiroshi
H
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8397, Japan. fuji@kuhp.kyoto-u.ac.jp
Higuchi
Toshihiro
T
Sato
Yukiyasu
Y
Nishioka
Yoshihiro
Y
Zeng
Bin-Xiang
BX
Yoshioka
Shinya
S
Tatsumi
Keiji
K
Ueda
Masamichi
M
Maeda
Michiyuki
M
D000595:Amino Acid Sequence; D018946:Chemokine CCL5 / Q000502:physiology; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008666:Metalloendopeptidases / Q000502:physiology*; D045726:Metalloproteases / Q000502:physiology; D008969:Molecular Sequence Data; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000502:physiology; D014327:Trophoblasts / Q000502:physiology*; D014599:Uterus / Q000502:physiology
C515300:CCR1 protein, human; D018946:Chemokine CCL5; D058851:GPI-Linked Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; C482089:LVRN protein, human; D045726:Metalloproteases; D018819:Dipeptidyl Peptidase 4; C058479:carboxypeptidase M; D008666:Metalloendopeptidases