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GnRH analogs reduce invasiveness of human breast cancer cells

  • Preclinical Study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Objective

Bone, besides lung and liver, is one of the most preferential metastatic target sites for breast cancers. Although the precise molecular mechanisms underlying this preference need to be elucidated, it appears that bone microenvironments possess unique biological features that enable circulating cancer cells to home, survive and proliferate, and destroy bone. The majority of human breast cancers and in addition most breast cancer cell lines express GnRH receptors. Their proliferation is time- and dose-dependently reduced by GnRH-I and GnRH-II agonists by counteracting of the mitogenic signal transduction.

Methods

We have established a coculture system of different breast cancer cell lines stable transfected with red fluorescence (DS-Red) and human primary osteoblasts (hOB) or MG63 human osteosarcoma cells to analyze tumor cell invasion to bone.

Results

We could show that breast cancer cell invasion was increased when cocultured with hOB or MG63. Treatment with GnRH-I and GnRH-II analogs reduced the ability to invade a reconstituted basement membrane (Matrigel) and to migrate in response to the cellular stimulus. Searching for the molecular mechanisms we found that GnRH treatment reduces expression of the osteoblast derived chemokine SDF-1 by hOB or MG63 cells cocultured with breast cancer cells.

Conclusion

These data represent the first report that the activation of tumor GnRH receptors reduces the metastatic potential of breast cancer cells. The crosstalk between metastatic breast cancer cells and bone is critical to the development and progression of bone metastases. Disruption of this interaction will allow us to design mechanism-based effective and specific therapeutic interventions for bone metastases.

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Acknowledgements

We are grateful to Zentaris (Frankfurt, Germany) for supplying the GnRH-I antagonist Cetrorelix and to Ferring Pharmaceuticals (Copenhagen, Denmark) for the gift of the GnRH-I agonist Triptorelin. This work was supported by the Deutsche Krebshilfe, Dr. Mildred Scheel Stiftung.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Georg-August-University, Robert-Koch-Street 40, D-37075, Göttingen, Germany

    Julia von Alten, Stefanie Fister, Hiltrud Schulz, Volker Viereck, Günter Emons & Carsten Gründker

  2. Department of Trauma Surgery, Georg-August-University, D-37070, Göttingen, Germany

    Karl-Heinz Frosch

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  1. Julia von Alten
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  2. Stefanie Fister
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Correspondence to Carsten Gründker.

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von Alten, J., Fister, S., Schulz, H. et al. GnRH analogs reduce invasiveness of human breast cancer cells. Breast Cancer Res Treat 100, 13–21 (2006). https://doi.org/10.1007/s10549-006-9222-z

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  • DOI: https://doi.org/10.1007/s10549-006-9222-z

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