To promote PDAC development heparanase acts through augmented release of HS-bound growth factors, removal of extracellular barriers for invasion (13–16, 25) and creation of tumor-stimulating “aseptic” inflammatory conditions, i.e., increased production of IL-6 (a key cytokine driving pancreatic tumorigenesis) by heparanase-stimulated tumor associated macrophages (TAM) (26). Here, HPSE is linked to neoplasm.