Alterations and role of human cathepsin D in cancer metastasis.

Cathepsin D (Cath D) overexpression in breast cancer cells is associated with increased risk of metastasis in patients according to several clinical studies. The amino acid sequence of Cath D in two breast cancer cell lines was normal, but glycosylation appears to be different with more acidic isoforms. Transfection of a human cDNA Cath D expression vector increases the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intravenously injected into nude mide. The mechanism of Cath-D-induced metastasis seems to require maturation of the proenzyme, mostly in large acidic compartments identified as phagosomes. Cath D is mitogenic in different cell types, and different substrates (growth inhibitors, precursors of growth factors, etc.) are proposed to mediate this activity.