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First published online March 12, 2004
doi: 10.1242/10.1242/jcs.00971


Journal of Cell Science 117, 1319-1328 (2004)
Published by The Company of Biologists 2004
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Research Article

Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts

Martin Bilban1,2,3,*, Nassim Ghaffari-Tabrizi2,*, Edith Hintermann1, Sandra Bauer5, Sylvia Molzer3, Cristina Zoratti4, Roland Malli4, Andrew Sharabi1, Ursula Hiden2, Wolfgang Graier4, Martin Knöfler5, Fritz Andreae2, Oswald Wagner3, Vito Quaranta1 and Gernot Desoye2,{ddagger}

1 Department of Cell Biology, The Scripps Research Institute, North Torrey Pines Road, La Jolla, 92037 CA, USA
2 Clinic of Obstetrics and Gynecology, Karl Franzens University Graz, Auenbruggerplatz 14, 8036 Graz, Austria
3 Institute for Laboratory Medicine, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
5 Clinic of Obstetrics and Gynecology, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
4 Institute for Medical Biochemistry, Karl-Franzens-University of Graz, Harrachgasse 21/III, 8010 Graz, Austria

{ddagger} Author for correspondence (e-mail: gernot.desoye{at}kfunigraz.ac.at)

Accepted 5 November 2003

Trophoblast invasion of the uterine extracellular matrix, a critical process of human implantation and essential for fetal development, is a striking example of controlled invasiveness. To identify molecules that regulate trophoblast invasion, mRNA signatures of trophoblast cells isolated from first trimester (high invasiveness) and term placentae (no/low invasiveness) were compared using U95A GeneChip microarrays yielding 220 invasion/migration-related genes. In this `invasion cluster', KiSS-1 and its G-protein-coupled receptor KiSS-1R were expressed at higher levels in first trimester trophoblasts than at term of gestation. Receptor and ligand mRNA and protein were localized to the trophoblast compartment. In contrast to KiSS-1, which is only expressed in the villous trophoblast, KiSS-1R was also found in the extravillous trophoblast, suggesting endocrine/paracrine activation mechanisms. The primary translation product of KiSS-1 is a 145 amino acid polypeptide (Kp-145), but shorter kisspeptins (Kp) with 10, 13, 14 or 54 amino acid residues may be produced. We identified Kp-10, a dekapeptide derived from the primary translation product, in conditioned medium of first trimester human trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca2+ levels in isolated first trimester trophoblasts. Kp-10 inhibited trophoblast migration in an explant as well as transwell assay without affecting proliferation. Suppressed motility was paralleled with suppressed gelatinolytic activity of isolated trophoblasts. These results identifed Kp-10 as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself.

Key words: Invasion, DNA microarray, Kisspeptins, Metastin, Trophoblast




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