To further investigate the interrelation between heparanase and MMPs, we transfected human breast carcinoma MDA-NB-231 cells, normally expressing moderate levels of heparanase [22], with either active or double mutant heparanase (active site Gln 225 and Gln 343 replaced by Ala) lacking enzymatic activity [41]. This evidence concerns the gene HPSE and breast carcinoma.