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

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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.

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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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Authors and Affiliations

  1. Max-Delbrück-Center for Molecular Medicine Berlin-Buch, R.-Rössle-Strasse 10, 13122, Berlin, Germany

    Jane Wenzel & Iduna Fichtner

  2. Experimental Pharmacology and Oncology Berlin-Buch GmbH (EPO GmbH), R.-Rössle-Strasse 10, 13122, Berlin, Germany

    Reiner Zeisig

  3. Charité, Medical Clinic IV, Nephrology, Campus Benjamin Franklin, Berlin, Germany

    Jane Wenzel

  4. Institute for Animal Pathology, Schönhauser Straße 62, 13127, Berlin, Germany

    Wolfram Haider

  5. Labor Sylvia Habedank, Postfach 49 01 52, 12281, Berlin, Germany

    Sylvia Habedank

Authors
  1. Jane Wenzel
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  2. Reiner Zeisig
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  3. Wolfram Haider
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  4. Sylvia Habedank
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  5. Iduna Fichtner
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Correspondence to Jane Wenzel.

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Wenzel, J., Zeisig, R., Haider, W. et al. Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation. Breast Cancer Res Treat 121, 13–22 (2010). https://doi.org/10.1007/s10549-009-0448-4

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  • DOI: https://doi.org/10.1007/s10549-009-0448-4

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