Expression of cathepsin D in primary and metastatic human melanoma and dysplastic nevi.
High levels of cytosolic cathepsin D expression have been associated with poor prognosis in breast cancer node-negative patients. In this work, we provide evidence that three cell lines established from human metastatic melanomas--IIB-MEL-J, IIB-MEL-LES, and IIB-MEL-IAN--express high levels of procathepsin D mRNA. IIB-MEL-J cells secreted into the conditioned media about 30% of the newly synthesized protein, which was active at acidic pH. Melanoma tumors arising in nude mice after injection of the three different cell lines expressed high levels of procathepsin D mRNA. Moreover, 13 human metastatic melanomas expressed variable levels of procathepsin D mRNA. To study the possible association between cathepsin D expression and melanoma development, samples corresponding to 10 primary tumors, 11 metastatic melanomas, 10 dysplastic nevi, 27 nevocellular nevi, and normal melanocytes were studied by immunohistochemistry for cathepsin D-specific staining. We found that cathepsin D was expressed in all of the dysplastic nevi and primary and metastatic melanomas tested but in only 18% of nevocellular nevi (five of 27), whereas normal melanocytes showed no cathepsin D expression. The overall data indicate that cathepsin D is expressed at a high level by melanoma cells, and because of its expression in preneoplastic lesions, it may be associated with melanoma development.
Podhajcer
O L
OL
Instituto de Investigaciones Bioquímicas Luis F. Leloir Fundación Campomar, Universidad de Buenos Aires, Argentina.
Bover
L
L
Bravo
A I
AI
Ledda
M F
MF
Kairiyama
C
C
Calb
I
I
Guerra
L
L
Capony
F
F
Mordoh
J
J
D002402:Cathepsin D / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned; D004416:Dysplastic Nevus Syndrome / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry / Q000235:genetics / Q000556:secondary*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D002402:Cathepsin D