HPSE and colorectal cancer: One study identified in a colorectal cancer model that heparanase involvement in chemoresistance is 2-fold: (i) heparanase induces syndecan-1 shedding directly and (ii) heparanase induces upregulation of matrix metalloprotease-9 (MMP-9), which induces the binding of heparin-binding epithelial growth factor-like factor (HB-EGF) to epidermal growth factor (EGF) receptor (EGFR) and downstream MEK ERK signaling, leading to 5-Fluorouracil resistance [151].