Procathepsin D in breast cancer: what do we know? Effects of ribozymes and other inhibitors.
Procathepsin D (pCD) is a major secreted glycoprotein in some human breast and other cancer cell lines. Several groups proposed that pCD served as a growth factor for these cell lines. Secreted pCD has been demonstrated in tissue section, tissue culture supernatants, carcinoma cytosols, and nipple aspirates. Moreover, several clinical studies suggested a potential role for this molecule in metastasis because its concentration in primary tumors correlated with an increased incidence of tumor metastases. In this paper, the effects of pCD were evaluated by proliferation in vitro and by mouse studies in vivo. Subsequent flow cytometry experiments showed the specificity of pCD binding to cancer cells. Cell cultivation showed that addition of either pCD or its activation peptide stimulates growth of cancer cells. These effects can be inhibited both in vitro and in vivo by anti-pCD antibodies. In addition, production of pCD can be inhibited by specifically designed ribozymes. This paper is focused on mitogenic effects of pCD, which seem to involve interaction of the activation peptide with as yet unidentified receptor. Different mechanisms by which pCD could promote development and spread of cancer cells are discussed.
Vetvicka
Vaclav
V
Department of Pathology and Laboratory Medicine, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA. vasek@louiseville.edu
Benes
Petr
P
Fusek
Martin
M
D000818:Animals; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002402:Cathepsin D / Q000502:physiology*; D002455:Cell Division; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D016337:RNA, Catalytic / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D017931:DNA Primers; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D016337:RNA, Catalytic; C058345:procathepsin D; D002402:Cathepsin D