title: The loss of endoglin promotes the invasion of extravillous trophoblasts.
abstract: Endoglin is a coreceptor for TGF-β, which is expressed in syncytiotrophoblasts. The soluble form of endoglin (sEng) has been observed to increase in the serum of preeclamptic patients. Several studies have shown that endoglin is involved in cancer invasion. However, the role of endoglin in extravillous trophoblasts (EVT), which have an invasive phenotype, remains unknown. The present study was designed to investigate the expression and role of endoglin in human EVT. We found that endoglin was mainly expressed on cytotrophoblasts within the cell column during the first trimester and its expression decreased in the EVT by immunohistochemistry and immunocytochemistry. The expression of endoglin significantly increased after treatment with TGF-β1 and TGF-β3 in the human EVT cell line, HTR-8/SVneo, as detected by semiquantitative RT-PCR. To investigate the role of endoglin in EVT, the stable knockdown of endoglin was performed by lentiviral short hairpin RNA transfection into the HTR-8/SVneo cells. Although proliferation was not affected, the motility and invasiveness of the HTR-8/SVneo cells significantly increased by the knockdown of endoglin. Both the mRNA expression and secretion of urokinase-type plasminogen activator significantly increased in endoglin knockdown cells. The secretion of sEng was very low in HTR-8/SVneo, and the treatment of endoglin knockdown cells with 10 ng/ml sEng had no effect on their invasiveness. Therefore, the suppression of sEng was not involved in the increased invasiveness of endoglin knockdown cells. These results suggested that EVT increased their invasive function as a result of decreasing expression of transmembrane endoglin.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya Graduate University School of Medicine, and Department of Maternal and Perinatal Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Mano
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kotani
authors.forename: Kiyozumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Sumigama
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Iwase
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D000071063:Endoglin; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases