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

Martin Bilban, Nassim Ghaffari-Tabrizi, Edith Hintermann, Sandra Bauer, Sylvia Molzer, Cristina Zoratti, Roland Malli, Andrew Sharabi, Ursula Hiden, Wolfgang Graier, Martin Knöfler, Fritz Andreae, Oswald Wagner, Vito Quaranta, Gernot Desoye

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1319-1328
Number of pages10
JournalJournal of cell science
Volume117
Issue number8
DOIs
StatePublished - Mar 15 2004

Keywords

  • DNA microarray
  • Invasion
  • Kisspeptins
  • Metastin
  • Trophoblast

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Bilban, M., Ghaffari-Tabrizi, N., Hintermann, E., Bauer, S., Molzer, S., Zoratti, C., Malli, R., Sharabi, A., Hiden, U., Graier, W., Knöfler, M., Andreae, F., Wagner, O., Quaranta, V., & Desoye, G. (2004). Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. Journal of cell science, 117(8), 1319-1328. https://doi.org/10.1242/jcs.00971