Targeting Mast Cells Tryptase in Tumor Microenvironment: A Potential Antiangiogenetic Strategy

Figure 1

Tryptase, released after MCs activation of c-KitR/SCF-mediated, acting on PAR-2 by its proteolytic activity, has angiogenic activity stimulating both human vascular endothelial and tumor cell proliferation in paracrine manner, helping tumor cell invasion and metastasis. In cancer treatment, tryptase may represent a promising target by tryptase inhibitors (gabexate mesylate, nafamostat mesylate, tranilast) due to their potential antiangiogenic activity. c-KitR, c-Kit receptor; PAR-2, proteinase-activated receptor-2; VEGFR, vascular endothelial growth factor receptor; SCF, stem cell factor, VEGF, vascular endothelial growth factor; NHERF-1, Na+/H+ exchanger regulatory factor-1; MEKK-1, mitogen-activated protein kinase/extracellular signal-related kinase-1; MEKK-4, mitogen-activated protein kinase/extracellular signal-related kinase-4; JNK, c-Jun N-terminal kinase; c-Jun, Jun protooncogene; SAPK, mitogen-activated protein kinase-9; GEF, rho/rac guanine nucleotide exchange factor; Rho, rhodopsin transcription termination factor; SOS, SOn of sevenless protein; Grb2, growth factor receptor-bound protein 2; Shc, Shc transforming protein kinase; Ras, Ras protein kinase; Raf, Raf protein kinase; mitogen-activated protein kinase/extracellular signal-related kinase-1/2; Erk, Elk-related tyrosine kinase; DAG, Diacylglycerol; IP-3, inositol triphosphate; PK-C, protein kinase-C; COX-2, cyclooxygenase-2; PGE2, prostaglandin E2; PGES-1, prostaglandin E synthase-1; PK-A, protein kinase-A.