Defining the roles of ADAM proteases in trophoblast biology
Defining the roles of ADAM proteases in trophoblast biology
Dr. Alex G. Beristain, M Aghababaei, L De Lucca, S Perdu, H Le
| Dr. Alex G. Beristain | alexander.beristain@ubc.ca |
Establishment of the placenta is a pivotal event in early pregnancy that bridges maternal and fetal circulatory systems via complex cellular interactions. At the cellular level, placentation requires progenitor trophoblasts located within chorionic villi to terminally differentiate into specialized subtypes of trophoblasts that play essential roles vascular-remodelling, fetal-maternal immune-tolerance, nutrient/waste exchange and endocrine function. Progenitor cell differentiation into highly invasive uterine infiltrating trophoblasts (called extravillous trophoblasts, EVTs) or into multinucleated cellular
structures (called the syncytiotrophoblast: synCT) are key cellular processes that enable placental function. My group is examining the importance of members of the A Disintegrin And Metalloproteinase (ADAM) family of proteases in regulating human trophoblast biology. ADAMs are multi-functional proteins important in regulating cell proliferation, survival, and invasion; their intrinsic proteolytic activities and integrin-mediated interactions direct molecular events like cell surface shedding of substrates (i.e. growth factors and their receptors), extracellular matrix (ECM) remodelling, as well as cell-cell and cell-matrix adhesion. For these reasons, ADAMs are attractive gene candidates for regulating trophoblast differentiation. We have defined a role for ADAM12 in driving progenitor differentiation into invasive EVTs. We also provide evidence that ADAM12-directed E-cadherin shedding potentiates synCT formation. Moreover, recent efforts have identified two additional ADAM proteases, ADAM8 and ADAM28, as key proteases linked to EVT column formation. Together, this work establishes the importance of ADAM gene members in controlling placental development.