The molecular mechanisms underlying heparanase induction in tumor cells are not entirely clear but involve epigenetic alterations (i.e., DNA methylation), hormones, oncogenes, and transcriptional/posttranscriptional regulation by elements (3ʹ‐UTR, enhancer, insulator) that activate or suppress the HPSE promoter.12, 45, 136. This evidence concerns the gene HPSE and neoplasm.