Induction of apoptotic or lytic death in an ovarian adenocarcinoma cell line by antibodies generated against a synthetic N-terminal extracellular domain gonadotropin-releasing hormone receptor peptide.
A polyclonal antiserum was generated in ovariectomized sheep against a synthetic peptide corresponding to amino acids 5-17 of the deduced mouse pituitary gonadotropin-releasing hormone (GnRH) receptor. Antipeptide antibodies did not bind native cells, but did react strongly with a human ovarian cancer cell line (OVCAR-3) reportedly sensitive to GnRH. Growth of cultured OVCAR-3 cells was specifically suppressed by antipeptide serum. This was attributed in part to programmed death (chromatin condensation and DNA fragmentation) of cells by antibody-induced apoptosis. Antibodies also exhibited a cytolytic effect (lactate dehydrogenase release) toward OVCAR-3 cells in the presence of the complement. Endometria of passively immunized mice lacked development; thus, antipeptide antibodies evidently recognize Mullerian duct derivatives. Experiments are in progress to determine whether the putative antigen is a variant of the pituitary GnRH receptor or a largely dissimilar protein. Effector-functional antibodies could be useful in the management of ovarian or uterine neoplasia.
Ackerman
R C
RC
Department of Animal Science, University of Wyoming, Laramie 82071.
Johnson
G A
GA
Van Kirk
E A
EA
Asirvatham
A L
AL
Murdoch
W J
WJ
D000230:Adenocarcinoma / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology*; D011966:Receptors, LHRH / Q000276:immunology*; D012756:Sheep; D014407:Tumor Cells, Cultured
D007106:Immune Sera; D010446:Peptide Fragments; D011966:Receptors, LHRH