title: Kisspeptin-10 inhibits stromal-derived factor 1-induced invasion of human endometrial cancer cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gynecology and Obstetrics, Georg-August-University, Göttingen, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Schmidt
authors.forename: Maike
authors.initials: M
authors.lastname: Haase
authors.forename: Elke
authors.initials: E
authors.lastname: Ziegler
authors.forename: Günter
authors.initials: G
authors.lastname: Emons
authors.forename: Carsten
authors.initials: C
authors.lastname: Gründker
mesh_terms: D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018920:Coculture Techniques; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000473:pathology; D005260:Female; D006801:Humans; D059648:Kisspeptins / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D010006:Osteoblasts / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; C106628:KISS1 protein, human; D059648:Kisspeptins