The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on bloodborne metastasis in vivo

Ralf J. Ludwig; Susanne Alban; Roxana Bistrian; Wolf-Henning Boehncke; Roland Kaufmann; Reinhard Henschler; Jens Gille

doi:10.1160/TH05-07-0515

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 95(03): 535-540
DOI: 10.1160/TH05-07-0515

Cellular Proteolysis and Oncology

Schattauer GmbH

The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on bloodborne metastasis in vivo

Ralf J. Ludwig

¹Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

,

Susanne Alban

²Pharmaceutical Institute, Christian-Albrechts-University, Kiel, Germany

,

Roxana Bistrian

³Institute for Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Service, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

,

Wolf-Henning Boehncke

¹Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

,

Roland Kaufmann

¹Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

,

Reinhard Henschler

³Institute for Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Service, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

,

Jens Gille

¹Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

› Institutsangaben

Abstract

Summary

Ample evidence suggests that many of the in vivo anti-metastatic effects by heparins reflect their actions on P-selectin-mediated binding. We hypothesized that the ability of widely used heparins and derivatives to interfere with P-selectin-dependent tumour cell interactions under flow in vitro could be used to identify anticoagulants with advanced inhibitory functions on experimental blood-borne metastasis in vivo. To test this assumption, the impact of unfractionated heparin, the low-molecular-weight heparins (LMWH) nadroparin and enoxaparin, and the synthetic pentasaccharide fondaparinux on P-selectin-dependent tumour interactions in vitro and metastasis formation in vivo were evaluated. Our data revealed that these commonly used anticoagulants widely differ in their potential to interfere with P-selectinmediated cell binding. Importantly, the superior inhibitory capacity on P-selectin function of unfractionated heparin and LMWH nadroparin as opposed to LMWH enoxaparin and synthetic heparin pentasaccharide fondaparinux strongly correlated to the inhibitory potency of each in inhibiting experimental lung metastasis in vivo. Hence, P-selectin inhibition may constitute a valuable feature to identify anticoagulants that are suitable for anticancer therapy.

Keywords

Anticoagulants - heparin - P-selectin - neoplasm metastasis - melanoma

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Referenzen

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