Thrombin induces tumor growth, metastasis, and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype.
The association of idiopathic venous thrombosis with occult cancer is generally recognized. However, it has not been fully appreciated that thrombin generated during thrombosis can augment the malignant phenotype. Thrombin activates tumor cell adhesion to platelets, endothelial cells, and subendothelial matrix proteins; enhances tumor cell growth; increases tumor cell seeding and spontaneous metastasis; and stimulates tumor cell angiogenesis. These mechanisms are reviewed. Evidence is also presented to support the hypothesis that thrombin serves to preserve dormant tumor cells in individuals, preventing host eradication. It is proposed that tumor malignancy may be regulated by a procoagulant/anticoagulant axis.
Nierodzik
Mary Lynn
ML
New York University School of Medicine, Department of Medicine/Hematology, 550 First Avenue, New York, New York 10016, USA.
Karpatkin
Simon
S
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001792:Blood Platelets / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D008168:Lung / Q000473:pathology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010641:Phenotype; D016032:Randomized Controlled Trials as Topic; D044463:Receptor, PAR-1 / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D020246:Venous Thrombosis
D000925:Anticoagulants; D044463:Receptor, PAR-1; D013917:Thrombin