Cancer and thrombosis in women - molecular mechanisms.
Both women and men with cancer are at increased risk for developing venous thromboembolism (VTE), a propensity that has been known for many years. Until recently it was assumed, however, that the association between cancer and thrombosis is an epiphenomenon - not causally related to the transforming malignant events. The pathophysiology of thrombosis in patients with cancer is complex involving multiple tumor-related and host-related factors. Several recent studies have provided strong evidence that activation of blood coagulation, perhaps most often mediated by tissue factor (TF)-rich microparticles (MPs), is linked directly to oncogene-induced malignant transformation. In addition, the development of VTE, either before or concurrent with the diagnosis of cancer, appears to predict an aggressive behavior of a tumor, and correlates with increased tumor angiogenesis and early onset of distant metastasis. The regulation of expression of TF in tumor cells is controlled at the molecular level by several oncogenes, as appears to be true for cyclooxygenase-2 (COX-2), an important regulator of platelet function and plasminogen activator inhibitor type 1 (PAI-1), an inhibitor of fibrinolysis. In addition, engagement of protease-activated receptors (PARs) by the TF-factor VIIa complex, factor Xa and/or thrombin, have now been shown to be important for tumor growth, angiogenesis and metastasis. Targeting blood clotting reactions in cancer, therefore, may provide a unique approach to cancer treatment.
Rickles
Frederick R
FR
Departments of Medicine, Pediatrics and Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA. frederick.rickles@noblis.org
D000925:Anticoagulants / Q000627:therapeutic use; D001777:Blood Coagulation / Q000235:genetics; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000097:blood* / Q000235:genetics / Q000628:therapy; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000235:genetics / Q000473:pathology*
D000925:Anticoagulants; D013925:Thromboplastin