Modulation of CA-125 tumor marker shedding in ovarian cancer cells by erlotinib or cetuximab.
OBJECTIVE
The EGF receptor tyrosine kinase inhibitor erlotinib and the EGF receptor antibody cetuximab were investigated with respect to their antiproliferative effect in vitro and their influence on the synthesis and secretion of the tumor marker CA-125 in ovarian carcinoma and human peritoneal mesothelial (HPMC) cells.


METHODS
Ovarian cancer cell lines and HPMC were cultured in vitro under the usual conditions. CA-125 surface expression was detected by a living cell radio-immunoassay. CA-125 concentration shed into supernatant medium was determined using a microparticle enzyme immunoassay.


RESULTS
Proliferation was inhibited by erlotinib in a dose-dependent manner in 4/5 cell lines but in none of the HPMCs. Only the erlotinib-sensitive cell lines also responded by decreasing surface density of CA-125. Release of CA-125 into the supernatant medium was independent of its surface density and was increased by erlotinib treatment in all but HTB77 cancer cells but not in HPMCs. Very similar results were obtained when the EGFR antibody cetuximab was used in place of erlotinib.


CONCLUSIONS
The results indicate that the effects observed were a consequence of EGFR inhibition. The influence exerted by erlotinib or cetuximab treatment on shedding and cell surface density of CA-125 leads us to conclude that CA-125 blood levels measured during therapy might not correctly indicate changes in tumor size.
Marth
Christian
C
Department of Obstetrics and Gynecology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Christian.marth@i-med.ac.at
Egle
Daniel
D
Auer
Doris
D
Rössler
Julia
J
Zeimet
Alain G
AG
Vergote
Ignace
I
Daxenbichler
Günter
G
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D018394:CA-125 Antigen / Q000096:biosynthesis / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D011863:Radioimmunoassay
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018394:CA-125 Antigen; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab