Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125.
CA125 is a mucin commonly employed as a diagnostic marker for epithelial ovarian cancer. Induction of humoral responses to CA125 leads to increased survival times in patients with this form of cancer, suggesting a potential role for this mucin in tumor progression. In this study, oligosaccharides linked to CA125 derived from the human ovarian tumor cell line OVCAR-3 were subjected to rigorous biophysical analysis. Sequencing of the O-glycans indicates the presence of both core type 1 and type 2 glycans. An unusual feature is the expression of branched core 1 antennae in the core type 2 glycans. CA125 is also N-glycosylated, expressing primarily high mannose and complex bisecting type N-linked glycans. High mannose type glycans include Man5-Man9GlcNAc2. The predominant N-glycans are the biantennary, triantennary, and tetraantennary bisecting type oligosaccharides. Remarkably, the N-glycosylation profiles of CA125 and the envelope glycoprotein gp120 (derived from H9 lymphoblastoid cells chronically infected with HIV-1) are very similar. The CA125-associated N-glycans have also recently been implicated in crucial recognition events involved in both the innate and adaptive arms of the cell-mediated immune response. CA125 may therefore induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression. Immunotherapy directed against CA125 may attenuate these immunosuppressive effects, leading to the prolonged survival of patients with this extremely serious form of cancer.
Department of Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AY, United Kingdom.
Nyet
N
Kui Wong
Richard L
RL
Easton
Maria
M
Panico
Mark
M
Sutton-Smith
Jamie C
JC
Morrison
Frank A
FA
Lattanzio
Howard R
HR
Morris
Gary F
GF
Clark
Anne
A
Dell
Manish S
MS
Patankar
D018394:CA-125 Antigen / Q000032:analysis / Q000737:chemistry* / Q000276:immunology; D002236:Carbohydrate Conformation; D005260:Female; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006031:Glycosylation; D006801:Humans; D007108:Immune Tolerance; D008358:Mannose / Q000032:analysis; D015394:Molecular Structure; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000276:immunology*; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D016339:Spectrometry, Mass, Fast Atom Bombardment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D018394:CA-125 Antigen; D009844:Oligosaccharides; D011134:Polysaccharides; D005643:Fucose; D001616:beta-Galactosidase; D008358:Mannose