Role of procathepsin D activation peptide in prostate cancer growth

BACKGROUND. Enzymatically inactive procathepsin D secreted from cancer cell s has been confirmed to play a role in breast cancer development. We focuse d on prostate cancer and the role of activation peptide in mitogenic activi ty. METHODS. Synthetic peptides and monoclonal antibodies raised against indivi dual fragments of activation peptide were employed. Cell proliferation was measured by MTT (3-[4,5-dimethylthiatol-2-yl]-2,5-diphenyl tetrazolium brom ide) assay or by in vivo growth in nude mice. RESULTS. We demonstrated that the growth factor activity of activation pept ide is localized in amino-acid region 27-44. In addition, both anti-activat ion peptide and anti-27-44 peptide antibodies administered in vivo inhibite d the growth of human prostate tumors in mice. CONCLUSIONS. Based on these data, we hypothesize that the interaction of pr ocathepsin D activation peptide with an unknown receptor is mediated by ami no-acid sequence 27-44. This interaction leads in certain types of tumor to a proliferation and higher motility. Blocking of this interaction by antib odies or antagonists might be a valuable tool in prostate cancer inhibition . (C) 2000 Wiley-Liss, Inc.