Anti-human procathepsin D activation peptide antibodies inhibit breast cancer development.
Enzymatically inactive procathepsin D secreted from cancer cells has been confirmed to play a role in development of human breast cancer. In the present study, we focused on the role of activation peptide which was in our preliminary studies suggested to be most probably responsible for mitogenic activity of procathepsin D. Using synthetic fragments and antibodies raised against individual fragments, we demonstrated that the growth factor activity of activation peptide is localized in a nine amino acid stretch (AA 36-44) of activation peptide and moreover both anti-activation peptide and anti-27-44 peptide antibodies administered in vivo inhibited the growth of human breast tumors in athymic nude mice. Taking into account our previous results and presented data, we hypothesize that the interaction of procathepsin D activation peptide with an unknown surface receptor is mediated by a sequence 36-44 plus close vicinity. We also propose that this interaction leads in certain types of tumor derived cell lines to proliferation and higher motility. Blocking of the interaction of activation peptide by specific antibodies or antagonists might be a valuable tool in breast cancer inhibition.
Vetvicka
V
V
Department of Pathology, School of Medicine, University of Louisville, KY 40292, USA.
Vetvickova
J
J
Fusek
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D002402:Cathepsin D / Q000276:immunology* / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement; D004792:Enzyme Precursors / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D004792:Enzyme Precursors; D010446:Peptide Fragments; C058345:procathepsin D; D002402:Cathepsin D