Fibrinolytic mechanisms in tumor growth and spreading

Abstract

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.

<p>The Prognostic Value of Combination of Plasma Fibrinogen and CA19-9 in Non-Distant Metastatic Breast Cancer Patients Undergoing Surgery</p>

“…26 Generated stroma furnishes connective tissue and new blood vessels which assist malignant tumor to absorb nutrients, grow, and spread. 27 Second, fibrinogen can bind to aIIbβ3 integrin to mediate the aggregation of tumor cells and platelets to form microthrombi. The microthrombi can serve as a barrier to protect tumor cells from natural killer cell elimination.…”

Clinical significance of coagulation factors in operable colorectal cancer

“…In the present study, PT, fibrinogen, FDP and D-dimer affected the overall survival of patients. Fibrin remodeling is involved in numerous steps of metastasis and has been shown to perform a crucial role in the formation of new vessels (42) Cross-linked fibrin in the ECM serves as a stable framework for endothelial cell migration during angiogenesis and for tumor cell migration during invasion (43). Knockout mouse models have also revealed the importance of fibrin remodeling in tumor growth and metastasis (44).…”

Plasma from Cancer Patients Featuring a Characteristic Protein Composition Mediates Protection against Apoptosis

“…1), as observed specifically in plasma of cancer patients, are caused by transglutaminase activity and have been described as indicative for tumor-associated fibrin deposition and fibrinolysis (7). Fibrinolysis is mediated mainly via the plasma protease plasmin (8), which exerts pleiotropic effects (24,25). Generally, plasma proteases, like metalloproteinases and plasmin, are capable of activating growth factors by cleavage of their inert proforms, a process essential during morphogenesis and chronic disease, e.g.…”