ALTERATIONS AND ROLE OF HUMAN CATHEPSIN-D IN CANCER METASTASIS

Cathepsin D (Cath D) overexpression in breast cancer cells is associat ed with increased risk of metastasis in patients according to several clinical studies. The amino acid sequence of Cath D in two breast canc er cell lines was normal, but glycosylation appears to be different wi th more acidic isoforms. Transfection of a human cDNA Cath D expressio n vector increases the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intravenously injected into nude mide. The mech anism of Cath-D-induced metastasis seems to require maturation of the proenzyme, mostly in large acidic compartments identified as phagosome s. Cath D is mitogenic in different cell types, and different substrat es (growth inhibitors, precursors of growth factors, etc.) are propose d to mediate this activity.