Fibrinolytic mechanisms in tumor growth and spreading

The high prevalence of hypercoagulative states in cancer patients has been known for more than a century. Venous thrombosis in gastric cancer was described by Trousseau in 1865 [55]. In 1878, Billroth observed intravascular thrombus formation in association with metastasis [4]. Thrombohemorrhagic complications regularly occur in patients with disseminated malignancy and are related to an increase in fibrinogen and fibrin turnover.During the past decade, clinicians have witnessed considerable advances in the understanding of fibrinolysis. Initially centered on the role as part of a dynamic, hemostatic balance, research began to unravel the pathophysiological contribution of fibrinolysis to tumor progression. The mechanisms of tumor invasion and metastasis formation in cancer are of critical importance, since metastasis is the major cause of treatment failure and death. It has been suggested that cell-associated proteolytic enzymes contribute to tumor aggressiveness [11, 22, 23]. Fibrinolytic mechanisms are involved in a number of physiological processes in which tissue degradation and remodeling occurs. These include disruption of the ovarian follicle during ovulation and blastocyst implantation. These events in part resemble the invasive growth of cancer [37, 47]. Inspired by this hypothesis, the role of fibrinolytic processes in tumor invasion is under intensive study.Abbreviations AML acute myelogenous leukemia - APL acute promyelocytic leukemia - FDP fibrin degradation products - FGF fbroblast growth factor - GM-CSF granulocytemacrophage colony stimulating factor - IL-3 interleukin 3 - IFN- interferon- - M-CSF macrophage-colony stimulating factor - PA plasminogen activator - PAI plasminogen activator inhibitor - TAM tumor-associated macrophage - TNF tumor necrosis factor - tPA tissue plasminogen activator - uPA urokinase-type plasminogen activator