Possible role of procathepsin D in human cancer.

For the past ten years, our research has been focused on elucidating the mechanism by which procathepsin D (pCD) impacts cancer development. Various studies have shown that pCD is overexpressed and secreted by numerous cancer cell lines. After secretion, it exhibits "growth hormone-like" activity on cancerous cells but the exact mechanism of this mitogenic activity is not yet understood. The activation peptide of pCD (APpCD) (which is cleaved off upon activation of the zymogen) is responsible for the mitogenic function of pCD. Various in vitro and in vivo studies support our theory that the APpCD interacts with both parent and neighborhood cancer cells and thus functions as an autocrine mitogen. We propose a model of pCD mitogenic function and also some possible approaches for treatment and prevention of certain types of cancer.