Introduction

Despite pioneer reports in the nineteenth century the interactions between the components of the hemostatic system and cancer have so far been studied without a really integrated approach and no true experimental–clinical cross-talk has been established.

Tumour growth and dissemination is a multistep process which goes from oncogenic transformation to progression and local growth, vascularization, detachment of tumour cells from the primary and invasion of capillary or lymphatic vessels, transport, arrest in capillary beds, adhesion to vessel wall, extravasation and growth at distant sites. All these steps involve different interactions with the components of the hemostatic system, which have been clarified mainly in in vitro approaches during the past 30 years. Tumour cells have been demonstrated as the source of procoagulant, fibrinolytic, platelet aggregation activities, adhesion processes with leukocytes and endothelial cells, and interactions with tumour-associated macrophages. In particular, clinical and experimental evidence suggests that blood platelets are involved at several steps of the tumour dissemination cascade. In this sequence of events, the adhesion of tumour cells to the vessel wall seems to be favoured by the gathering of activated platelets in the surroundings. More than 40 years ago, platelet–tumour cell emboli were observed in microcinematography experiments in rabbits and human pathological specimens, suggesting the possible involvement of platelets in tumour dissemination. The discovery that thrombocytopenia, induced by antiplatelet serum or neuroaminidase treatment, reduced experimental metastasis in mice, further supported this hypothesis.