Results from clinical studies indicate a strong association between thromboembolism and solid malignancy. Being central to blood coagulation and displaying a number of cellular postclotting activities, the serine protease thrombin has been localized within or adjacent to malignant tissues possibly associated with fibrin(oid) deposits. Thrombin proteolytically activates its cellular receptors including the prototypic protease-activated receptor 1 which is expressed by various tumor cells. Current molecular and cellular studies provide mounting evidence that the activation of protease-activated receptor(s) is the main mechanism whereby thrombin exerts its modulating effects on the malignant phenotype including tumor growth, local progression, and distant metastasis. A detailed under standing of the molecular interplay between thrombin, thrombin receptor(s) and cancer biology may be helpful to develop new therapeutic approaches consisting of the suppression of thrombin receptor(s) in malignancy.
Biomedical Reviews 2003; 14: 9-22.
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