Heparanase is upregulated in many tumor types and has been associated with increased metastasis and poor prognosis in breast cancer.(10) It has been suggested that much of heparanase function is regulated by its remodeling of the extracellular matrix and by its effects on cell signaling.(49) Our findings provide new insight into how heparanase regulates tumor behavior via upregulation of syndecan-1 shedding. This evidence concerns the gene HPSE and breast cancer.