Cathepsin D in breast cancer: from molecular and cellular biology to clinical applications.
Cathepsin D is a ubiquitously expressed lysosomal protease. Initially synthesized as an inactive precursor of 52 kD (pro-cathepsin D), the enzyme is subsequently converted to its active forms by proteolytic processing. Breast cancer cells, unlike normal cells, secrete high levels of pro-cathepsin D; this abnormal secretion is due to both overexpression of the gene and altered processing of the protein. Recent transfection experiments indicate that overexpression of cathepsin D can increase the metastatic potential of tumor cells in nude mice. This study complements clinical studies, which have shown than high cathepsin D concentrations in the cytosol of primary breast cancers may be predictive of subsequent metastasis, particularly for patients with axillary node-negative tumors. These results, and the potential mechanisms by which cathepsin D may promote metastasis, are considered here.
Rochefort
H
H
Unité Hormones et Cancer (U 148) INSERM, University of Montpellier 1, France.
Capony
F
F
Garcia
M
M
D001943:Breast Neoplasms / Q000175:diagnosis / Q000503:physiopathology*; D002402:Cathepsin D / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D002402:Cathepsin D