title: EMILIN1 represents a major stromal element determining human trophoblast invasion of the uterine wall.
abstract: The detection of EMILIN1, a connective tissue glycoprotein associated with elastic fibers, at the level of the ectoplacental cone and trophoblast giant cells of developing mouse embryos (Braghetta et al., 2002) favored the idea of a structural as well as a functional role for this protein in the process of placentation. During the establishment of human placenta, a highly migratory subpopulation of extravillous trophoblasts (EVT), originating from anchoring chorionic villi, penetrate and invade the uterine wall. In this study we show that EMILIN1, produced by decidual stromal and smooth muscle uterine cells, is expressed in the stroma and in some instances as a gradient of increasing concentration in the perivascular region of modified vessels. This distribution pattern is consistent with the haptotactic directional migration observed in in vitro functional studies of freshly isolated EVT and of the immortalized HTR-8/SVneo cell line of trophoblasts. Function-blocking monoclonal antibodies against alpha4-integrin chain and against EMILIN1 as well as the use of EMILIN1-specific short interfering RNA confirmed that trophoblasts interact with EMILIN1 and/or its functional gC1q1 domain via alpha4beta1 integrin. Finally, membrane type I-matrix metalloproteinase (MT1-MMP) and MMP-2 were upregulated in co-cultures of trophoblast cells and stromal cells, suggesting a contributing role in the haptotactic process towards EMILIN1.
authors.affiliation: Divisione di Oncologia Sperimentale 2, CRO-IRCCS, 33081 Aviano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Spessotto
authors.forename: Roberta
authors.initials: R
authors.lastname: Bulla
authors.forename: Carla
authors.initials: C
authors.lastname: Danussi
authors.forename: Oriano
authors.initials: O
authors.lastname: Radillo
authors.forename: Marta
authors.initials: M
authors.lastname: Cervi
authors.forename: Giada
authors.initials: G
authors.lastname: Monami
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
authors.forename: Roberto
authors.initials: R
authors.lastname: Doliana
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D002824:Chorionic Villi / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D034741:RNA, Small Interfering / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014327:Trophoblasts / Q000502:physiology*; D014599:Uterus / Q000473:pathology*
chemical_list: D039041:Integrin alpha4beta1; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C030340:elastin microfibril interface located protein; D053504:Matrix Metalloproteinases, Membrane-Associated