Over past ten years our work has been focused on the mechanism of procathepsin D role in cancer development. It has been shown that procathepsin D (pCD) is over expressed and secreted by numerous cancer cell lines. After secretion it exhibits “growth hormone-like” activity on cancer cells. The mechanism of this mitogenic function has not yet been understood. In our work we have identified the peptidic part of pCD – the activation peptide (which is cleaved off upon activation of the zymogen) to be responsible for mitogenic function of procathepsin D. Numerous both in vitro and in vivo studies had supported our theory that the activation peptide is interacting with both parent and neighborhood cancer cells as an autocrine mitogen. Based on these findings, we propose a model of pCD mitogenic function and possible approaches for treatment and prevention of certain types of cancer.
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