title: Regulation of human extravillous trophoblast function by membrane-bound peptidases.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8397, Japan. fuji@kuhp.kyoto-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Sato
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Bin-Xiang
authors.initials: BX
authors.lastname: Zeng
authors.forename: Shinya
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Keiji
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ueda
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Maeda
mesh_terms: 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
chemical_list: 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