Heparanase can promote an aggressive tumor behavior also through an indirect mechanism by enhancing HSPG ectodomain proteolytic shedding, which converts a membrane proteoglycan co-receptor into a soluble paracrine bioactive effector able to potentiate the activity of HS-binding growth factors (e.g., VEGF and HGF) [91]. Here, HSPG2 is linked to neoplasm.