Using myeloma cell lines, it was found that: (i) within the nucleus, heparanase is present in the soluble fraction, and it is also bound to insoluble chromatin; (ii) the presence of nuclear heparanase enhances acetylation of histone H3 and promotes an open chromatin conformation; (iii) heparanase binds the promoter region of syndecan-1, MMP9, and CCND1, three genes whose expression is upregulated by heparanase; and (iv) heparanase increases phosphorylation of PTEN, leading to enhanced PTEN stability and thereby diminishing its function as a tumor suppressor [18]. Here, PTEN is linked to plasma cell myeloma.