HPSE and melanoma: Heparanase can also interfere with gene transcription directly by binding to nuclear DNA38 or indirectly by controlling histone H3 methylation patterns.39, 40 The overexpression of heparanase in melanoma cell lines prompted us to study its role on cancer cells per se.38, 41 Accordingly, melanoma MDA‐MB‐435s cells and MV3 cells expressed remarkably high levels of endogenous heparanase (Figure 1A).