title: Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2.
abstract: Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander University Erlangen-Nürnberg, Loschgestr. 15, 91054, Erlangen, Germany, Fabian.Fahlbusch@uk-erlangen.de.
authors.forename: Fabian B
authors.initials: FB
authors.lastname: Fahlbusch
authors.forename: Matthias
authors.initials: M
authors.lastname: Ruebner
authors.forename: Hanna
authors.initials: H
authors.lastname: Huebner
authors.forename: Gudrun
authors.initials: G
authors.lastname: Volkert
authors.forename: Hannah
authors.initials: H
authors.lastname: Bartunik
authors.forename: Ilona
authors.initials: I
authors.lastname: Winterfeld
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.forename: Carlos
authors.initials: C
authors.lastname: Menendez-Castro
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Noegel
authors.forename: Ines
authors.initials: I
authors.lastname: Marek
authors.forename: David
authors.initials: D
authors.lastname: Wachter
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Sven
authors.initials: S
authors.lastname: Kehl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
mesh_terms: D000328:Adult; D000650:Amnion / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D017359:HELLP Syndrome / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D010922:Placenta Diseases / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D051381:Rats; D014327:Trophoblasts / Q000378:metabolism*; D014470:Umbilical Cord / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C477000:GKN1 protein, human; C503073:GKN2 protein, human; D036361:Peptide Hormones