Translator Disclaimer
2 April 2014 Extravillous Trophoblast-Associated ADAM12 Exerts Pro-Invasive Properties, Including Induction of Integrin Beta 1-Mediated Cellular Spreading
Author Affiliations +
Abstract

ADAM12, consisting of a membrane-bound (ADAM12L) and a secreted (ADAM12S) form, is expressed exclusively in regenerating and developing tissue as well as in certain cancer types. Strong ADAM12 expression levels have been noticed in the human placenta, and deregulated ADAM12S levels were associated with various pregnancy-related disorders including pre-eclampsia and intrauterine growth restriction. However, the role of ADAM12 in trophoblast motility has not been investigated so far. Hence, the present study aimed to investigate the specific function of the protease by using different primary trophoblast cell models. Immunofluorescence and Western blot analyses of first trimester placental tissue and differentiating primary first trimester cytotrophoblasts (CTBs) indicated strong upregulation of both of the ADAM12 isoforms during extravillous trophoblast differentiation. Functional assays involving short interfering RNA (siRNA)-mediated knockdown studies in primary CTBs and first trimester explant cultures revealed a significant repression of trophoblast motility upon partial loss of ADAM12. Conversely, isoform-specific overexpression in the ADAM12-negative trophoblast cell line SGHPL-5 enhanced the invasive capacity of these cells. We further confirmed proteolytic activity of trophoblast-derived ADAM12S by demonstrating its potential to degrade insulin-like growth factor-binding protein 3. Finally, we suggest that ADAM12S exerts its pro-migratory function in trophoblasts by inducing integrin beta 1-mediated cellular spreading.

Katarzyna Biadasiewicz, Valerie Fock, Sabine Dekan, Katharina Proestling, Philipp Velicky, Sandra Haider, Martin Knöfler, Camilla Fröhlich, and Jürgen Pollheimer "Extravillous Trophoblast-Associated ADAM12 Exerts Pro-Invasive Properties, Including Induction of Integrin Beta 1-Mediated Cellular Spreading," Biology of Reproduction 90(5), (2 April 2014). https://doi.org/10.1095/biolreprod.113.115279
Received: 25 October 2013; Accepted: 1 March 2014; Published: 2 April 2014
JOURNAL ARTICLE
PAGES

This article is only available to subscribers.
It is not available for individual sale.
+ SAVE TO MY LIBRARY

SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top