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

M Bilban, N Ghaffari-Tabrizi… - Journal of cell …, 2004 - journals.biologists.com
M Bilban, N Ghaffari-Tabrizi, E Hintermann, S Bauer, S Molzer, C Zoratti, R Malli, A Sharabi
Journal of cell science, 2004journals.biologists.com
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 thisinvasion cluster', KiSS-1 and its G-protein-coupled …
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.
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