Biological and clinical significance of cathepsin D in breast cancer.

Cathepsin D, an aspartyl protease of lysosomes, is overproduced and hypersecreted by breast cancer cells. The prognostic value of its immunoassay in breast cancer cytosol is reviewed from the first retrospective clinical studies available, which show a strong correlation between high concentrations of cathepsin D in the cytosol of primary tumor and further occurrence of metastasis. This new prognostic factor is induced by estrogen in hormone dependent breast cancer but expressed at a high level in hormone independent breast cancer and appears to be independent of other more classical factors. Its value in node negative patients varies according to the studies. In nude mice, transfection of cathepsin D cDNA into tumor cells increases their metastatic potential, suggesting that overexpression of this protease may be one of the factors responsible for metastasis in human breast cancer. The mechanism by which this protease might facilitate metastasis in vivo is still unknown, even though cathepsin D has the potential to initiate a proteolytic cascade, to degrade extracellular matrix and to liberate FGFs like growth factors from the matrix. These studies should stimulate the search for new therapeutical agents in order to inhibit cathepsin D action.