Analysis of the interaction of procathepsin D activation peptide with breast cancer cells.
Cathepsin D, a lysosomal aspartic proteinase, is secreted in the form of enzymatically inactive proenzyme by many types of human breast cancer tissue and exerts mitogenic activity toward these tissues. Flow cytometry was used to test the binding of procathepsin D purified from the secretion of the breast cancer cell line ZR-75-1 to human breast cancer cells. No previously known surface antigens or soluble M6P-R or anti-M6P-R antibodies were found to inhibit the specific binding of procathepsin D-FITC. Similarly, none of these potential inhibitors was found to inhibit growth factor activity of procathepsin D. Our results indicate that procathepsin D growth factor activity is mediated by a new, previously unknown receptor moiety and that the binding activity can be localized in position 27-44 of the activation peptide of procathepsin D. Furthermore, in vivo experiments indicate that treatment with anti-procathepsin D antibodies can reverse the growth of human breast tumors in athymic nude mice.
Vetvicka
V
V
Department of Pathology, School of Medicine, University of Louisville, KY 40292, USA. v0vetv01@homer.louisville.edu
Vetvickova
J
J
Hilgert
I
I
Voburka
Z
Z
Fusek
M
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D002402:Cathepsin D / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*
D000906:Antibodies; D004792:Enzyme Precursors; D005456:Fluorescent Dyes; D017527:Receptor, IGF Type 2; D017978:Receptors, Growth Factor; C058345:procathepsin D; D002402:Cathepsin D; D016650:Fluorescein-5-isothiocyanate