By sustaining continuous activation and polarization of macrophages that supply cancer-promoting cytokines (i.e., IL-1, IL-6, IL-1β, TNF-α, MIP-2, IL-10, iNOS), heparanase (produced primarily by inflamed epithelium) may participate in creating a pro-tumorigenic microenvironment, characterized by enhanced NFκB and p38-MAPK signaling (71), that supports the development and progression of gastric cancer. This evidence concerns the gene HPSE and gastric cancer.