The role of fibrin in tumor metastasis

Abstract

A volume of data that has accumulated for over a century has suggested that fibrin may facilitate the persistence and progression of malignancy. Techniques that have been developed recently have shown that fibrin is indeed a component of the connective tissue stroma in human malignancy but in only a few tumor types. However, therapeutic intervention studies with drugs that limit thrombin activity or enhance fibrinolysis have shown favorable clinical effects in at least one such tumor type. These favorable findings affirm the concept that cause-and-effect relationships do, in fact, exist between thrombin generation with fibrin formation and tumor progression, and suggest that a rational basis exists for the design of future drug intervention trials that target reactions relevant to specific tumor types. These findings also provide a basis for the design of experiments capable of defining further the role of fibrin in the integrity of these tumor types. Because fibrinogen is found much more commonly than fibrin in the connective tissue of a variety of human malignancies, attention might reassumably be directed to determining the possible contribution of this molecule as well as of fibrin to tumor progression.

Host Markers and Prognosis in Recurrent Rectal Carcinomas Treated with Radiotherapy

“…In patients with Hodgkin's disease (22), nasopharyngeal (23), colon or non-small lung cancer (24), elevated fibrinogen or fibrin split products are associated with adverse survival. Experimental data suggest that fibrin assists tumor progression by formation of stroma (25,26), and trials are currently testing antithrombotic drugs in cancer treatment (27). Although many questions still remain unanswered, fibrinogen may be an important, measurable indicator of metastatic progression.…”

Kinetics of Fibrinopeptide Release by Thrombin as a Function of CaCl2 Concentration: Different Susceptibility of FPA and FPB and Evidence for a Fibrinogen Isoform-Specific Effect at Physiological Ca2+ Concentration

“…The fibrinogen-fibrin transition and FP release have also been extensively studied for their involvement in other pathophysiological processes such as angiogenesis and metastatic spread (27,28). An increased rate of FPA release has been associated with various malignancies (29).…”

Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse

“…2 In addition to their function in clot formation, Fg and fibrin play roles in other pathophysiological processes, such as infection, 3 wound healing, 4,5 and clot retraction. 6 Further, both Fg and fibrin have been implicated in the progression of certain types of tumors, 7 and in the severity of atherosclerosis. 8 Congenital afibrinogenemia (MIM no.…”