Biological and clinical significance of cathepsin D in breast cancer.

Cathepsin D is an acidic lysosomal protease present in all cells. In breast cancer cells, pro-cathepsin D expression and secretion are markedly increased and its processing is altered. This protease is induced by estrogens and growth factors. In vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans in acidic microenvironment. 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 lymph node-negative tumors. These results suggest that derouting and overexpression of cathepsin D plays an important role in invasion and metastasis of breast cancer cells.