Figure 9: Neutrophils and coagulation during small intestinal tumorigenesis.
The Apc mutation induces growth of polyps in the small intestine of APCMin/+ mice and results in defects in gut permeability, ultimately leading to bacterial and/or bacterial products translocation in the systemic circulation. LPS induces upregulation of C3aR on neutrophils (HDNs and LDNs), thereby enhancing the interaction with C3a produced via alternative complement activation. These events result in NET induction, which form a scaffold for the recruitment of components of the coagulation cascade. By interacting with the circulating neutrophils, the formed clot induces LDNs, which can further fuel coagulation in a positive feedback loop by undergoing NETosis and can exert protumorigenic functions.
