Role of procathepsin D activation peptide in prostate cancer growth.
BACKGROUND
Enzymatically inactive procathepsin D secreted from cancer cells has been confirmed to play a role in breast cancer development. We focused on prostate cancer and the role of activation peptide in mitogenic activity.


METHODS
Synthetic peptides and monoclonal antibodies raised against individual fragments of activation peptide were employed. Cell proliferation was measured by MTT (3-[4,5-dimethylthiatol-2-yl]-2,5-diphenyl tetrazolium bromide) assay or by in vivo growth in nude mice.


RESULTS
We demonstrated that the growth factor activity of activation peptide is localized in amino-acid region 27-44. In addition, both anti-activation peptide and anti-27-44 peptide antibodies administered in vivo inhibited the growth of human prostate tumors in mice.


CONCLUSIONS
Based on these data, we hypothesize that the interaction of procathepsin D activation peptide with an unknown receptor is mediated by amino-acid sequence 27-44. This interaction leads in certain types of tumor to a proliferation and higher motility. Blocking of this interaction by antibodies or antagonists might be a valuable tool in prostate cancer inhibition.
Vetvicka
V
V
Department of Pathology, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA. Vasek@louisville.edu
Vetvickova
J
J
Fusek
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D002402:Cathepsin D / Q000276:immunology / Q000502:physiology*; D002455:Cell Division; D002846:Chromatography, Affinity; D004792:Enzyme Precursors / Q000276:immunology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005562:Formazans / Q000737:chemistry; D005780:Gelatin; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D010446:Peptide Fragments / Q000276:immunology / Q000502:physiology*; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D013778:Tetrazolium Salts / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004792:Enzyme Precursors; D005562:Formazans; D010446:Peptide Fragments; D013778:Tetrazolium Salts; C079782:MTT formazan; D005780:Gelatin; C058345:procathepsin D; D002402:Cathepsin D