Summary

Ample evidence suggests that many of the in vivo anti-metastaticeffects by heparins reflect their actions on P-selectin-mediatedbinding.We hypothesized that the ability of widely used heparinsand derivatives to interfere with P-selectin-dependent tumourcell interactions under flow in vitro could be used to identify anticoagulantswith advanced inhibitory functions on experimentalblood-borne metastasis in vivo.To test this assumption, the impactof unfractionated heparin, the low-molecular-weight heparins(LMWH) nadroparin and enoxaparin,and the synthetic pentasaccharidefondaparinux on P-selectin-dependent tumour interactionsin vitro and metastasis formation in vivo were evaluated. Our data revealed that these commonly used anticoagulantswidely differ in their potential to interfere with P-selectinmediatedcell binding.Importantly,the superior inhibitory capacityon P-selectin function of unfractionated heparin and LMWHnadroparin as opposed to LMWH enoxaparin and synthetic heparinpentasaccharide fondaparinux strongly correlated to theinhibitory potency of each in inhibiting experimental lung metastasisin vivo. Hence, P-selectin inhibition may constitute a valuablefeature to identify anticoagulants that are suitable for anticancertherapy.