title: CD9 suppresses human extravillous trophoblast invasion.
abstract: During human placentation, the extravillous trophoblast (EVT) invades the maternal decidua and reconstructs maternal spiral arteries. However, the precise mechanisms that control EVT behavior have not yet been elucidated in detail. CD9 has been reported to be a cell-motility-related molecule. Since we previously observed that CD9 was expressed on human EVT, we examined the possible involvement of CD9 in the invasion process of EVT. Placental and umbilical samples were obtained from patients who underwent legal abortions, normal delivery, or hysterectomy. The expression of CD9 at the implantation site and on isolated EVT from a villous explant culture, an EVT-derived immortalized cell line, Swan71, and HUVEC was examined by immunocytochemical staining, flow cytometry, and RT-PCR. The effects of anti-CD9 functional antibody (ALB6) on EVT and Swan71 cell invasion were further examined by matrigel invasion assay along with shRNAmir gene knockdown treatment. CD9 was highly expressed on EVT at the boundary region of EVT invasion and intravascular EVT. EVT and Swan71 cell invasions were promoted by ALB6 or shRNAmir treatment. CD9 expression on Swan71 cells was reduced under hypo-oxygenic conditions, while its expression was increased by the co-culture with HUVEC. These findings suggest that CD9 could attenuate EVT invasion under the influence of an oxygen environment and maternal endothelial cells, proposing that CD9 is a potential regulator of human placental formation.
authors: Department of Gynecology and Obstetrics, National Hospital Organization Osaka National Hospital, Japan; Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors: Hisanori
authors: H
authors: Matsumoto
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan; Department of Obstetrics and Gynecology, Otsu Red Cross Hospital, Japan.
authors: Yukiyasu
authors: Y
authors: Sato
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors: Akihito
authors: A
authors: Horie
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors: Koh
authors: K
authors: Suginami
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors: Hirohiko
authors: H
authors: Tani
authors: Department of System Chemotherapy and Molecular Sciences, Kyoto University Graduate School of Pharmaceutical Sciences, Japan.
authors: Akira
authors: A
authors: Hattori
authors: Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Japan.
authors: Yoshihiko
authors: Y
authors: Araki
authors: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Japan.
authors: Kyosuke
authors: K
authors: Kagami
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan; National Hospital Organization Kyoto Medical Center, Japan.
authors: Ikuo
authors: I
authors: Konishi
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan; Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Japan. Electronic address: fuji@med.kanazawa-u.ac.jp.
authors: Hiroshi
authors: H
authors: Fujiwara
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D002824:Chorionic Villi / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D034741:RNA, Small Interfering; D060245:Tetraspanin 29 / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D060245:Tetraspanin 29
keywords: CD9; Extravillous trophoblast; Invasion; Oxygen concentration; Vascular remodeling