Figure 1

Positive feedback loops promoting mast cell-mediated angiogenesis in cancer. A wide variety of tumors are known to secrete SCF, which induces mast cell migration in vivo. Mast cell activation by SCF induces MMP-9 production, which clips membrane-bound SCF from the tumor cell surface, increasing the bioavailability of SCF. Activated mast cells produce tryptase, which can enhance tumor cell COX activity via the PAR-2 receptor. COX-mediated PGE-2 production can activate mast cells to secrete VEGF, promoting tumor angiogenesis.