Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin Α5β1 Is a Modulator of Extravillous Trophoblast Functions
Shemona Rattila,
Caroline E. E. Dunk,
Michelle Im,
Olga Grichenko,
Yan Zhou,
Maria Yanez-Mo,
Sandra M. Blois,
Kenneth M. Yamada,
Offer Erez,
Nardhy Gomez-Lopez,
Stephen J. Lye,
Boris Hinz,
Roberto Romero,
Marie Cohen,
Gabriela Dveksler
Affiliations
Shemona Rattila
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA
Caroline E. E. Dunk
Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5T 3H7, Canada
Michelle Im
Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada
Olga Grichenko
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA
Yan Zhou
Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, USA
Maria Yanez-Mo
Department of Molecular Biology, Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
Sandra M. Blois
Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, and the Charité-Universitätsmedizin Berlin, AG GlycoImmunology, 13125 Berlin, Germany
Kenneth M. Yamada
Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892, USA
Offer Erez
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, MD 20892, USA, and Detroit, MI 48201, USA
Nardhy Gomez-Lopez
Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, MD 20892, USA, and Detroit, MI 48201, USA
Stephen J. Lye
Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5T 3H7, Canada
Boris Hinz
Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada
Roberto Romero
Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, MI 48109, USA
Marie Cohen
Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, 1206 Geneva, Switzerland
Gabriela Dveksler
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA
Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin 5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to 51 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to 51 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.
