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Immunoradiometric assay of pro-cathepsin D in breast cancer cytosol: relative prognostic value versus total cathepsin D.

Abstract
In breast cancer cell lines, the maturation of pro-cathepsin D into enzymatically active cathepsin D is altered, leading to its increased secretion. In order to specifically assay pro-cathepsin D (52 kD form) in breast cancer cytosol, we monitored a solid phase sandwich radioimmunoassay using D9H8 and D7E3 monoclonal antibodies raised against human pro-cathepsin D from MCF7 cells. Pro-cathepsin D was assayed in 108 primary breast cancer cytosols in which total cathepsin D was previously found to be correlated with metastasis. Pro-cathepsin D concentrations were found to be correlated with total cathepsin D and with lymph node invasion, and was slightly higher in premenopausal patients. By contrast, Cox multiparametric analysis showed that pro-cathepsin D status had no prognostic value for survival, or metastasis free survival contrary to total cathepsin D status. This first study shows the technical validity of the pro-cathepsin D assay but indicates that it has less value as a prognostic marker than total cathepsin D. This study also shows that the proportion of pro-cathepsin D recovered in vivo (1-6%) is much less than that produced in cell lines and suggests that the secreted pro-enzyme might be activated in the tumour extracellularly or following its reinternalisation.
AuthorsJ P Brouillet, F Spyratos, K Hacene, J Fauque, G Freiss, F Dupont, T Maudelonde, H Rochefort
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 29A Issue 9 Pg. 1248-51 ( 1993) ISSN: 0959-8049 [Print] England
PMID8343262 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Enzyme Precursors
  • procathepsin D
  • Cathepsin D
Topics
  • Biomarkers, Tumor (analysis)
  • Breast Neoplasms (enzymology, mortality)
  • Cathepsin D (analysis)
  • Cytosol (enzymology)
  • Enzyme Precursors (analysis)
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoradiometric Assay (methods)
  • Lymphatic Metastasis
  • Prognosis
  • Reproducibility of Results
  • Retrospective Studies

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