The role of fibrinogen and related fragments in tumour angiogenesis and metastasis

Angiogenesis, the development of new blood vessels from existing vasculature, involves the migration, proliferation and differentiation of endothelial cells and is crucial for the growth and mestastasis of tumours. A specific association between cancer and the haemostatic system has long been recognised. Haemostatic mechanisms regulate blood flow by controlling platelet adhesion and fibrin deposition, and a number of haemostatic proteins have been shown to regulate angiogenesis, either directly, by interacting with endothelial cells themselves, or indirectly, by interacting with other regulators of angiogenesis. The polypeptide fibrinogen is the central protein in the haemostasis pathway and is found deposited in the majority of human and experimental animal tumours. In this review, the evidence for the ability of fibrinogen and various protein/peptide fragment derivatives to modulate angiogenic mechanisms in vitro and to affect tumour growth and metastasis in vivo is discussed.