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First published online October 30, 2006
doi: 10.1242/10.1242/jcs.03232

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EMILIN1 represents a major stromal element determining human trophoblast invasion of the uterine wall

Paola Spessotto^1,*, Roberta Bulla^2,*, Carla Danussi¹, Oriano Radillo³, Marta Cervi¹, Giada Monami^1,, Fleur Bossi², Francesco Tedesco³, Roberto Doliana¹ and Alfonso Colombatti^1,4,5,

¹ Divisione di Oncologia Sperimentale 2, CRO-IRCCS, 33081 Aviano, Italy
² Dipartimento di Fisiologia e Patologia, University of Trieste, Trieste, Italy
³ Laboratorio di Analisi, IRCCS Burlo Garofalo, University of Trieste, Trieste, Italy
⁴ Dipartimento di Scienze e Tecnologie Biomediche, University of Udine, Udine, Italy
⁵ MATI Center of Excellence, University of Udine, 35100 Udine, Italy

Author for correspondence (e-mail: acolombatti{at}cro.it)

Accepted 29 August 2006

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 4-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 4ß1 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.

Key words: EMILIN1, 4 integrin, Trophoblast, Migration, MMP

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