Olbrich, TeresaTeresaOlbrichZiegler, ElkeElkeZieglerTuerk, GregorGregorTuerkSchubert, AntjeAntjeSchubertEmons, GuenterGuenterEmonsGruendker, CarstenCarstenGruendker2018-11-072018-11-072010https://resolver.sub.uni-goettingen.de/purl?gro-2/18261Objectives. The KiSS-1 gene product is absent or expressed at low level in metastatic breast cancer compared with their nonmetastatic counterparts. A deca-peptide derived from the KiSS-1 gene product, designated kisspeptin-10 (Kp-10), activates a receptor coupled to G alpha q subunits (GPR54 or KiSS-1R). In this study we have analyzed whether Kp-10 treatment affects bone-directed migration of GPR54-positive breast cancer cells. Methods. GPR54 expression was analyzed using immune cytochemistry. Bone-directed breast cancer cell invasion was measured by assessment of the breast cancer cell migration rate through an artificial basement membrane. Chemokine receptor CXCR4 and stromal cell-derived factor-1 (SDF-1) mRNA expression was quantified using semi-quantitative RT-PCR. CXCR4 protein expression and SDF-1 protein secretion were measured using the western blot technique. Results. Breast cancer cell invasion was increased when cocultured with MG63 osteoblast-like cells. Treatment with KP-10 reduced the ability to invade a reconstituted basement membrane and to migrate in response to the cellular stimulus. This effect was significant in a dose-window of 10(-9) M to 10(-11) M. Searching for the molecular mechanisms we found that KP-10 treatment significantly reduces expression of the chemokine receptor CXCR4 by the breast cancer cells. In addition, expression and secretion of its ligand SDF-1 by the MG63 cells were significantly reduced. Furthermore, SDF-1-induced CXCR4 signaling was down-regulated. Conclusions. These data represent the first report that KP-10 inhibits bone-directed migration of GPR54-positive breast cancer cells. In addition, we found evidence for a KP-10 dose-window effect. Furthermore, the SDF-1/CXCR4 system seems to be involved in the anti-migratory action of KP-10. (C) 2010 Elsevier Inc. All rights reserved.journal_article10.1016/j.ygyno.2010.08.01820832102000284556800030