Immunoradiometric assay of pro-cathepsin D in breast cancer cytosol: relative prognostic value versus total cathepsin D.
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.
Brouillet
J P
JP
Unité Hormones et Cancer (U 148) INSERM, Montpellier, France.
Spyratos
F
F
Hacene
K
K
Fauque
J
J
Freiss
G
G
Dupont
F
F
Maudelonde
T
T
Rochefort
H
H
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality; D002402:Cathepsin D / Q000032:analysis*; D003600:Cytosol / Q000201:enzymology*; D004792:Enzyme Precursors / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015592:Immunoradiometric Assay / Q000379:methods; D008207:Lymphatic Metastasis; D011379:Prognosis; D015203:Reproducibility of Results; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D004792:Enzyme Precursors; C058345:procathepsin D; D002402:Cathepsin D