Possible biological and translational significance of mast cells density in colorectal cancer

Figure 1 Close relationship between mast cells and angiogenesis-mediated tumor progression. FGF-2: Fibroblast growth factor-2; VEGF: Vascular endothelial growth factor; PDGF-β: Platelet-derived growth factor-β; EGF: Epidermal growth factor; IL: Interleukin; GM-CSF: Granulocyte/macrophage colony stimulating factor; TNF-α: Tumor necrosis factor-α; ECM: Extracellular matrix; MMP: Matrix metalloproteinase.

Figure 2 In both intestinal and endothelial cells, the tryptase/proteinase-activated receptor-2 and vascular endothelial growth factor/vascular endothelial growth factor receptor axes, induced by mast cells, lead to tumor angiogenesis and intestinal cell growth. Note that targeting mast cells with molecular agents (c-KitR tyrosine kinase and tryptase inhibitors) could prevent angiogenesis-mediated colorectal cancer progression. 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 proto-oncogene; 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.