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Breast Cancer Research and Treatment

, Volume 121, Issue 1, pp 13–22 | Cite as

Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation

  • Jane Wenzel
  • Reiner Zeisig
  • Wolfram Haider
  • Sylvia Habedank
  • Iduna Fichtner
Preclinical study
First Online:
Received:
Accepted:

Abstract

The process of metastasis formation in cancer is not completely understood and is the main reason cancer therapies fail. Previously, we showed that dual liposomes simultaneously containing the hemostatic inhibitor, dipyridamole and the anticancer drug, perifosine potently inhibited metastasis, causing a 90% reduction in the number of lung metastases in a murine experimental metastasis model. To gain deeper insight into the mechanisms leading to the inhibition of metastasis by these dual liposomes, in the present study, the development of metastases by MT3 breast cancer cells in a mouse xenograft model was analyzed in more detail with regard to tumor cell settlement and metastatic growth. We found that the development of lung metastases by MT3 tumor cells is essentially dependent on the formation of fibrin clots as a precondition for the pulmonary arrest of tumor cells and the subsequent intravascular expansion of micrometastases before their invasion into the surrounding tissue.

Keywords

Intravasal micrometastases Breast cancer Fibrin clot Platelet aggregation Liposomes Lung metastases 
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Notes

Acknowledgments

This study was supported by the Federal Ministry of Education and Research of Germany (Biochance PLUS program; PTJ-BIO/0313601). We thank Prof. M. van der Giet for supporting the Ph.D. work of J.W. at the Charite Berlin; M. Becker and M. Lemm (MDC Berlin-Buch) for excellent performance of the animal experiments; and Lipoid GmbH Ludwigshafen for providing us with egg phosphatidylcholine.

Conflict of interest statement

All authors confirm that they have no potential conflict of interest, including any financial, personal, or other relationships with other people or organizations within that could inappropriately influence (bias) their work.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jane Wenzel
    • 1
    • 3
  • Reiner Zeisig
    • 2
  • Wolfram Haider
    • 4
  • Sylvia Habedank
    • 5
  • Iduna Fichtner
    • 1
  1. 1.Max-Delbrück-Center for Molecular Medicine Berlin-BuchBerlinGermany
  2. 2.Experimental Pharmacology and Oncology Berlin-Buch GmbH (EPO GmbH)BerlinGermany
  3. 3.Charité, Medical Clinic IV, NephrologyBerlinGermany
  4. 4.Institute for Animal PathologyBerlinGermany
  5. 5.Labor Sylvia HabedankBerlinGermany

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