Cathepsin D: a protease involved in breast cancer metastasis

Cathepsin D is an acidic lysosomal protease present in all cells. In Estrogen receptor positive and negative breast Cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, via possibly saturation of the Man-6-P/IGF-II receptor, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the Cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In patients, there is a significant correlation between high Cathepsin D concentrations in the cytosol of primary breast Cancer and development of metastasis. This marker is independent of Other prognostic factors and appears to be particularly useful in axillary node-negative tumors. Transfection of a human cDNA Cathepsin D expression vector under the control of SV40 promoter increases the metastatic potential of 3YA1-Ad12 rat tumorigenic cells when intravenously injected into nude mice. The mechanism of Cathepsin D-induced metastasis is currently unknown. These results indicate that overexpression of Cathepsin D might facilitate breast Cancer metastasis, suggesting new possible therapeutic approaches.