Antimetastatic effects associated with anticoagulant properties of heparin and chemically modified heparin species in a mouse mammary tumor model

Abstract

Fibrin deposits surrounding circulating tumor cells may protect them from mechanical trauma and destruction by the host immune system, and may facilitate microvascular entrapment required for metastasis. We report that heparin inhibited the clotting of plasma induced by mouse mammary carcinoma cells in a dose-dependent manner and blocked the production of experimental lung metastasis when administered i.p. at the time of intravenous injection of tumor cells. On the other hand, O/N-desulfated N-acetylated heparin did not exhibit anticoagulant properties and had no effects on metastasis formation. Similarly, reduction of metastasis was not seen with N-desulfated N-acetylated heparin, another chemically modified heparin which does not inhibit blood coagulation but has heparanase inhibitory activity. Our data demonstrate the existence of a strong association between antimetastatic and anticoagulant properties of heparin species in the present experimental system.