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PMID: 7980446 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mitogenic function of human procathepsin D: the role of the propeptide.

The Biochemical journal ·Vol. 303 ( Pt 3) ·1994-11-01 ·Pages 775-80

Fusek M, Vetvicka V

Abstract

The proform of cathepsin D is secreted by some human breast-cancer cell lines upon stimulation with oestrogen. In these cell lines, procathepsin D was described to act as an autocrine mitogen, and a correlation between the cathepsin D concentration in tumour tissues and poor prognosis for the patient was demonstrated in several independent investigations. In the present study, we focused on the mechanism of procathepsin D mitogenic activity. Procathepsin D isolated from secretions of ZR-75-1 breast-cancer cell line was used to test for mitogenic activity on a set of seven human cell lines. For nanomolar procathepsin D concentrations, we found a stronger dose-responsive cellular reaction in the case of several different human breast-cancer-derived cell lines. The mitogenic activity was not blocked by the inhibition of proteolytic activity nor by the inhibition of the interaction of procathepsin D with mannose-6-phosphate receptors. On the other hand, the addition of antibodies raised against the propeptide impaired the mitogenic activity of procathepsin D, and a synthetic peptide alone corresponding to the propeptide of procathepsin D produced similar effects, as did the zymogen molecule. The synthetic propeptide was shown to block partially the interaction of procathepsin D with the cellular surface. Our results indicate that the mitogenic function involves the propeptide of cathepsin D, which appears to be recognized by a surface receptor.

MeSH Terms
Cathepsin D/physiology Cell Division Enzyme Precursors/physiology Fluorescein-5-isothiocyanate Humans Hydrolysis Insulin-Like Growth Factor II/physiology Mitogens/physiology Peptides/physiology Tumor Cells, Cultured
Chemicals
Enzyme Precursors Mitogens Peptides Insulin-Like Growth Factor II procathepsin D Cathepsin D Fluorescein-5-isothiocyanate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Fusek M
Oklahoma Medical Research Foundation, Oklahoma City 73104.
Vetvicka V
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30 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3030775
Published
1994-11-01
Pages
775-80
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1137614
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3030775 PMC Full Text View journal details
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