Paclitaxel- and docetaxel-dependent activation of CA-125 expression in human ovarian carcinoma cells.
Taxanes represent a new class of antineoplastic agents that are being evaluated in several malignant tumors; they have been shown to induce a high remission rate and to prolong survival in ovarian cancer patients. However, CA-125 has been suggested to be an unreliable marker for monitoring response to paclitaxel therapy. Therefore, we were interested in whether taxanes may directly modulate CA-125 expression. Human ovarian carcinoma cell lines OVCAR-3, HOC-7, SKOV-6, 2780, 2774, and HTB-77 were treated with paclitaxel or docetaxel. Secreted, surface-associated, and cytosolic CA-125 were estimated by means of a sandwich solid-phase RIA or by immuno-flow cytometry. In addition to in vitro antiproliferative activity, paclitaxel and docetaxel augmented the expression of the tumor marker CA-125 in the three ovarian carcinoma cell lines, OVCAR-3, HOC-7, and SKOV-6, constitutively expressing this tumor marker. The three CA-125-negative cell lines, 2780, 2774, and HTB-77, did not respond to taxane treatment by expressing this tumor marker, although their proliferation was markedly inhibited. The taxane-mediated induction of CA-125 was found to be dependent on intact protein and RNA biosynthesis. However, CA-125 concentration was increased in the supernatant medium only and not on cell surface or cytosol. Our results demonstrate an in vitro activation of ovarian carcinoma cells in terms of CA-125 secretion by taxanes. This may explain the CA-125 fluctuations observed in vivo under paclitaxel treatment and may indicate that CA-125 is not a reliable tumor marker during taxane chemotherapy.
Marth
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C
Department of Obstetrics and Gynecology, Innsbruck University Hospital, Austria. christian.marth@dnr.uio.no
Zeimet
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AG
Widschwendter
M
M
Ludescher
C
C
Kaern
J
J
Tropé
C
C
Gastl
G
G
Daxenbichler
G
G
Dapunt
O
O
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018394:CA-125 Antigen / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000276:immunology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D018394:CA-125 Antigen; D009363:Neoplasm Proteins; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel