Fibroblasts in the TME are greatly modified by soluble factors produced by the tumor cells, thereby forming a tumor-reactive stroma, and may undergo differentiation into myofibroblasts and secrete additional growth factors, cytokines and chemokines, including: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and stromal-derived factor (SDF)-1, which act in both paracrine and autocrine manner7–11. This evidence concerns the gene VEGFA and neoplasm.