title: Polysialic acid enhances the migration and invasion of human cytotrophoblasts.
abstract: Polysialic acid (polySia) is a large, cell-surface linear homopolymer composed of α2,8-linked sialic acid residues. Most extensively studied in the nervous system, this unique glycan modulates development by enhancing cell migration and regulating differentiation. PolySia also functions in developing and adult immune systems and is a signature of many cancers. In this study, we demonstrated that human placental trophoblasts, an epithelial lineage, also display this glycan. Cytotrophoblasts and syncytiotrophoblasts expressed polySia in the first trimester and downregulated it during the course of pregnancy. PolySia promoted cytotrophoblast migration in an explant model of chorionic villous growth. Removal of this glycan also reduced cytotrophoblast penetration of basement membranes in an in vitro model of invasion. Finally, we showed that polySia was overexpressed in biopsies from patients with gestational trophoblastic diseases, including benign molar pregnancies and malignant choriocarcinomas. These results demonstrated, for the first time, functional roles for polySia during normal human placental development and implicated these unusual oligosaccharides in the unrestrained invasion of trophoblast tumors.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, RMB 902A, San Francisco, CA 94143-0665, USA. bethann.hromatka@gmail.com
authors.forename: Bethann S
authors.initials: BS
authors.lastname: Hromatka
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Drake
authors.forename: Mirhan
authors.initials: M
authors.lastname: Kapidzic
authors.forename: Haley
authors.initials: H
authors.lastname: Stolp
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Goldfien
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D002822:Choriocarcinoma / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011247:Pregnancy; D012794:Sialic Acids / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism
chemical_list: D012794:Sialic Acids; C021319:polysialic acid