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Kisspeptin-10 Inhibits Stromal-Derived Factor 1–Induced Invasion of Human Endometrial Cancer Cells

Schmidt, Elena; Haase, Maike; Ziegler, Elke PhD; Emons, Günter MD; Gründker, Carsten PhD

International Journal of Gynecological Cancer: February 2014 - Volume 24 - Issue 2 - p 210–217
doi: 10.1097/IGC.0000000000000050
Basic Science

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. We have established a coculture system of cells derived from different tumor entities and MG63 human osteoblastlike cells to analyze tumor cell invasion. Recently, we have shown that breast cancer cell invasion was dramatically increased when cocultured with MG63 cells.

Using this model, we have 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 migration rate through an artificial basement membrane in a modified Boyden chamber during coculture with MG63 cells or after treatment with SDF-1α, SDF-1β, or the combination of both SDF-1 isoforms. In addition, the role of SDF-1 in invasion of endometrial cancer cells was analyzed by blocking SDF-1 secretion during coculture with MG64 cells. 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. The MG63 coculture-induced increase of endometrial cancer cell invasion could be blocked by anti–SDF-1 antibodies. Treatment of endometrial cancer cells in monoculture (without MG63) with SDF-1α, SDF-1β, 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: Our findings suggest that SDF-1 plays a major role in endometrial cancer invasion. Stromal-derived factor 1–induced invasion can be inhibited by KP-10 treatment.

Department of Gynecology and Obstetrics, Georg-August-University, Göttingen, Germany.

Address correspondence and reprint requests to Carsten Gründker, PhD, Department of Gynecology and Obstetrics, Georg-August-University, Robert-Koch St 40, 37075 Göttingen, Germany. E-mail: grundker@med.uni-goettingen.de.

This study was supported by Deutsche Krebshilfe–Dr Mildred Scheel Stiftung (grant no. 108754).

The authors declare no conflicts of interest.

Received October 1, 2013

Received in revised form October 27, 2013

Accepted October 28, 2013

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.