Kisspeptin-10 - ein potenzieller Inhibitor der Invasion humaner Endometriumkarzinomzellen

Kisspeptin-10 - a potential inhibtor of the invasion of human endometrial cancer cells

by Elena Schmidt
Doctoral thesis
Date of Examination:2014-03-05
Date of issue:2014-02-24
Advisor:Prof. Dr. Carsten Gründker
Referee:Prof. Dr. Carsten Gründker
Referee:Prof. Dr. Claudia Binder
Referee:Prof. Dr. Michael P. Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-4353

 

 

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Abstract

English

Objectives: The cross talk between metastatic cancer cells and target sites is critical for the development and progression of metastases. Disruption of this interaction will allow to design mechanism-based effective and specific therapeutic interventions for metastases. An established coculture system of cells derived from different tumor entities and MG63 human osteoblastlike cells to analyze tumor cell invasion was used. With this model, it was now analyzed whether stromal-derived factor 1 (SDF-1) is responsible for human endometrial cancer cell invasion and whether kisspeptin-10 (KP-10) treatment affects SDF-1-induced invasion of endometrial cancer cells in vitro. Methods: Invasion was quantified by assessment of endometrial cancer cell invasionrate through an artificial basementmembrane in amodified Boyden chamber during coculture with MG63 cells or after treatment with SDF-1 beta, SDF-1 alpha, or the combination of both SDF-1 isoforms. Furthermore, the effects of KP-10 treatment on MG63 coculture-driven and SDF-1-induced invasion were analyzed. Results: Endometrial cancer cell invasion was significantly increased when cocultured with MG63 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 10^13 to 10^11 mol/L. During coculture, SDF-1 protein expression of MG63 cells was significantly increased. Treatment of endometrial cancer cells in monoculture (withoutMG63) with SDF-1 alpha, SDF-1 beta, or the combination of both isoforms resulted in a significant increase of endometrial cancer cell invasion. The SDF-1-induced increase of endometrial cancer cell invasion was significantly reduced after treatment with KP-10. Conclusions: The findings suggest that SDF-1 plays a major role in endometrial cancer invasion. Stromal-derived factor1-induced invasion can be inhibited by KP-10 treatment.
Keywords: kisspeptin-10; sdf-1; cxcr4; endometrial cancer; gpr54
 
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