Polysialic acid enhances the migration and invasion of human cytotrophoblasts

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.