Clotting factors in tumour tissue: implications for cancer therapy.
Considerable progress has been made recently in understanding the mechanisms and significance of coagulation activation in human malignancy. Neoplastic cells may activate coagulation reactions directly, that is through contact with coagulation factors; or indirectly by formation of cytokines capable of activating certain host cells such as macrophages or endothelial cells. Data suggest that at least two autoregulatory pathways involving components of coagulation and fibrinolysis pathways exist. In one of these, tumour cell procoagulants lead to generation of thrombin in the tumour periphery. Thrombin is a mitogen that may also contribute to tumour stoma formation. Alternatively, tumour cells may express urokinase responsible for generation of cell surface-related proteolysis that may facilitate tumour cell proliferation, invasion and metastasis. An appreciation of these diverse mechanisms may permit rational design of clinical trials of agents capable of interrupting relevant pathways.
Zacharski
L R
LR
Department of Medicine, Dartmouth Medical School, Hanover, NH 03756.
Memoli
V A
VA
Costantini
V
V
Wojtukiewicz
M Z
MZ
Ornstein
D L
DL
D000925:Anticoagulants / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013917:Thrombin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism
D000925:Anticoagulants; D000970:Antineoplastic Agents; D001779:Blood Coagulation Factors; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator