Fig. 7.

Model for inflammation as a unifying trigger predisposing to deregulated blood coagulation (thrombin gene expression) and tumor formation. Inflammatory stimuli can induce both tumor formation (simplified) and thrombin (F2) gene expression. This in turn leads to a disequilibrium of pro- and anticoagulatory activities (and thereby promotes tumor-associated thrombus formation) and drives protumorigenic cellular programs (in an autocrine and/or paracrine manner; SD unpublished). Tumor formation will thus be supported by the tumor-promoting properties of thrombin; vice versa, tumor formation elicits detrimental inflammatory responses [159], which in turn further promote tumorigenesis and p38 MAPK (p38)-mediated induction of thrombin gene expression. (Extracellular matrix (ECM), Reactive oxygen species (ROS), epithelial–mesenchymal transformation, mesenchymal–epithelial transformation (EMT/MET))