ABSTRACT
A link between cancer and the hemostatic system was fi rst recognized more than a century ago with the observation that cancer patients are prone to hemostatic derangements, such as thrombophlebitis and disseminated intravascular coagulation. Malignant human and experimental animal tumor cells frequently express procoagulant and fi brinolytic factors [e.g., tissue factor (TF), plasminogen activator (PA), plasminogen activator receptor] that are either absent or minimally expressed in the normal cells from which the transformed cell is derived (1-3). Additionally, tumor stromal cells often express either cellassociated or secreted hemostatic factors (e.g., PA) that may contribute to tumor growth and/or dissemination (4,5). Multiple clinical studies have shown that the expression of hemostatic factors by malignant and/or stromal cells is associated with more advanced disease and a worse prognosis for a variety of human cancers (1,2,4). These correlative fi ndings have suggested that the pattern of hemostatic factor expression might be useful
for establishing both clinical prognosis and optimal therapy. However, expression data alone provided no insight into whether there was a causal relationship between specifi c hemostatic factors and the malignant phenotype. This gap in our understanding of tumor biology has begun to be fi lled through detailed studies of animal models of cancer. It is increasingly clear that the relationship between hemostatic system components and cancer is not merely an epiphenomenon. Rather, hemostatic factors actively contribute to tumor progression. Much of the data supporting this view has come from analyses of gene-targeted mice with defects in specifi c hemostatic factors. Nearly all of the known coagulation and fi brinolytic factors as well as their receptors and inhibitors have been genetically disrupted or modifi ed in mice. Similarly, many genes essential for either platelet development or function have been selectively disrupted. Since many of these mutant animals are viable and can be studied well into adulthood, they have been an extraordinary resource in establishing the precise contribution of the hemostatic system to tumor growth and dissemination.
