Alterations and role of human cathepsin D in cancer metastasis.
Cathepsin D (Cath D) overexpression in breast cancer cells is associated with increased risk of metastasis in patients according to several clinical studies. The amino acid sequence of Cath D in two breast cancer cell lines was normal, but glycosylation appears to be different with more acidic isoforms. Transfection of a human cDNA Cath D expression vector increases the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intravenously injected into nude mide. The mechanism of Cath-D-induced metastasis seems to require maturation of the proenzyme, mostly in large acidic compartments identified as phagosomes. Cath D is mitogenic in different cell types, and different substrates (growth inhibitors, precursors of growth factors, etc.) are proposed to mediate this activity.
Rochefort
H
H
Institut National de la Santé et de la Recherche Médicale, (U. 148), Montpellier, France.
Liaudet
E
E
Garcia
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002402:Cathepsin D / Q000502:physiology*; D005260:Female; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D010587:Phagocytosis; D011379:Prognosis; D051381:Rats
D002402:Cathepsin D