title: Laeverin/aminopeptidase Q induces trophoblast invasion during human early placentation.
abstract: BACKGROUND
  In primate placenta, extravillous trophoblast (EVT) invades maternal tissue in temporally- and spatially-regulated fashions. We previously identified a novel placenta-specific cell-surface aminopeptidase, laeverin/aminopeptidase Q, which is expressed on EVT-lineage cells in the fetal membrane. Laeverin possesses a peptide-binding site that is evolutionally unique to primates, suggesting possible involvement of laeverin in a primate-specific phenomenon during placentation. Thus, this study was designed to elucidate the molecular characteristics and physiological roles of laeverin in human EVT.
  
  
  METHODS
  Placental tissues of various developmental stages were subjected to immunostaining and western blotting. Effects of siRNA and a soluble form of recombinant laeverin on EVT cells isolated from primary villous explant cultures were examined using Matrigel invasion assays and cell proliferation assays.
  
  
  RESULTS
  Laeverin was specifically immunolocalized to HLA-G-positive EVT in placentas from early and term pregnancy. In primary villous explant cultures, laeverin expression was induced on the cell surface of the outgrowing EVT. In western blotting, laeverin protein was detected as two distinct bands at 130 and 160 kDa along with a broad band ranging from 200 to 270 kDa. De-glycosylation treatment showed that these native laeverin isotypes are N-linked glycoproteins sharing a common 115-kDa core protein. In invasion assays, the reduction of laeverin expression by siRNA suppressed migration of the isolated EVT, while the soluble form of recombinant laeverin enhanced its migration.
  
  
  CONCLUSIONS
  Laeverin is a specific cell-surface marker for human EVT and plays a regulatory role in EVT migration.
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Horie
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Sato
authors.forename: Koh
authors.initials: K
authors.lastname: Suginami
authors.forename: Hisanori
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Masato
authors.initials: M
authors.lastname: Maruyama
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
mesh_terms: D015415:Biomarkers; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D059951:HLA-G Antigens; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010920:Placenta / Q000378:metabolism; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology*
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C482089:LVRN protein, human; D045726:Metalloproteases