Deciphering the molecular nature of ovarian cancer biomarker CA125

International Journal of Molecular Sciences

Volumn 13, Issue 8, 2012, Pages 10568-10582

  Weiland, Florian ^a   Martin, Karina ^a   Oehler, Martin K ^b   Hoffmann, Peter ^a  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Biomarker; CA125; Mass spectrometry; MUC16; Ovarian cancer

Indexed keywords

CA 125 ANTIGEN; TUMOR MARKER;

AMINO ACID SEQUENCE; CANCER DIAGNOSIS; CANCER GROWTH; HUMAN; MASS SPECTROMETRY; NUCLEOTIDE SEQUENCE; OVARY CANCER; PROGNOSIS; PROTEIN ANALYSIS; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; ANIMAL; FEMALE; METABOLISM; OVARIAN NEOPLASMS;

ANIMALS; CA-125 ANTIGEN; FEMALE; HUMANS; OVARIAN NEOPLASMS; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 84874047777     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms130810568     Document Type: Review

References (65)

1. Bast, R.C., Jr.; Feeney, M.; Lazarus, H.; Nadler, L.M.; Colvin, R.B.; Knapp, R.C. Reactivity of a monoclonal antibody with human ovarian carcinoma. J. Clin. Invest. 1981, 68, 1331-1317.
2. Bast, R.C., Jr.; Klug, T.L.; St John, E.; Jenison, E.; Niloff, J.M.; Lazarus, H.; Berkowitz, R.S.; Leavitt, T.; Griffiths, C.T.; Parker, L.; et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N. Engl. J. Med. 1983, 309, 883-887.
3. Muyldermans, M.; Cornillie, F.J.; Koninckx, P.R. CA125 and endometriosis. Hum. Reprod. Update 1995, 1, 173-187.
4. Jacobs, I.; Oram, D.; Fairbanks, J.; Turner, J.; Frost, C.; Grudzinskas, J.G. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br. J. Obstet. Gynaecol. 1990, 97, 922-929.
5. Bast, R.C., Jr.; Badgwell, D.; Lu, Z.; Marquez, R.; Rosen, D.; Liu, J.; Baggerly, K.A.; Atkinson, E.N.; Skates, S.; Zhang, Z.; et al. New tumor markers: CA125 and beyond. Int. J. Gynecol. Cancer 2005, 15 Suppl 3, S274-S281.
6. Menon, U.; Gentry-Maharaj, A.; Hallett, R.; Ryan, A.; Burnell, M.; Sharma, A.; Lewis, S.; Davies, S.; Philpott, S.; Lopes, A.; et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: Results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009, 10, 327-340.
7. Kui Wong, N.; Easton, R.L.; Panico, M.; Sutton-Smith, M.; Morrison, J.C.; Lattanzio, F.A.; Morris, H.R.; Clark, G.F.; Dell, A.; Patankar, M.S. Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125. J. Biol. Chem. 2003, 278, 28619-28634.
8. Patankar, M.S.; Jing, Y.; Morrison, J.C.; Belisle, J.A.; Lattanzio, F.A.; Deng, Y.; Wong, N.K.; Morris, H.R.; Dell, A.; Clark, G.F. Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125. Gynecol. Oncol. 2005, 99, 704-713.
9. Belisle, J.A.; Gubbels, J.A.; Raphael, C.A.; Migneault, M.; Rancourt, C.; Connor, J.P.; Patankar, M.S. Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125). Immunology 2007, 122, 418-429.
10. Zhang, J.Q.; Nicoll, G.; Jones, C.; Crocker, P.R. Siglec-9, a novel sialic acid binding member of the immunoglobulin superfamily expressed broadly on human blood leukocytes. J. Biol. Chem. 2000, 275, 22121-22126.
11. Belisle, J.A.; Horibata, S.; Jennifer, G.A.; Petrie, S.; Kapur, A.; Andre, S.; Gabius, H.J.; Rancourt, C.; Connor, J.; Paulson, J.C.; et al. Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol. Cancer 2010, 9, 118.
12. Seelenmeyer, C.; Wegehingel, S.; Lechner, J.; Nickel, W. The cancer antigen CA125 represents a novel counter receptor for galectin-1. J. Cell Sci. 2003, 116 (Pt 7), 1305-1318.
13. Demydenko, D.; Berest, I. Expression of galectin-1 in malignant tumors. Exp. Oncol. 2009, 31, 74-79.
14. Rump, A.; Morikawa, Y.; Tanaka, M.; Minami, S.; Umesaki, N.; Takeuchi, M.; Miyajima, A. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J. Biol. Chem. 2004, 279, 9190-9198.
15. Rodriguez, G.C.; Haisley, C.; Hurteau, J.; Moser, T.L.; Whitaker, R.; Bast, R.C., Jr.; Stack, M.S. Regulation of invasion of epithelial ovarian cancer by transforming growth factor-beta. Gynecol. Oncol. 2001, 80, 245-253.
16. O'Brien, T.J.; Tanimoto, H.; Konishi, I.; Gee, M. More than 15 years of CA 125: What is known about the antigen, its structure and its function. Int. J. Biol. Markers 1998, 13, 188-195.
17. Yin, B.W.; Lloyd, K.O. Molecular cloning of the CA125 ovarian cancer antigen: Identification as a new mucin, MUC16. J. Biol. Chem. 2001, 276, 27371-27375.
18. O'Brien, T.J.; Beard, J.B.; Underwood, L.J.; Dennis, R.A.; Santin, A.D.; York, L. The CA 125 gene: An extracellular superstructure dominated by repeat sequences. Tumour Biol. 2001, 22, 348-366.
19. McLemore, M.R.; Aouizerat, B. Introducing the MUC16 gene: Implications for prevention and early detection in epithelial ovarian cancer. Biol. Res. Nurs. 2005, 6, 262-267.
20. Hovig, E.; Rye, P.D.; Warren, D.J.; Nustad, K. CA 125: The end of the beginning. Tumour Biol. 2001, 22, 345-347.
21. O'Brien, T.J.; Beard, J.B.; Underwood, L.J.; Shigemasa, K. The CA 125 gene: A newly discovered extension of the glycosylated N-terminal domain doubles the size of this extracellular superstructure. Tumour Biol. 2002, 23, 154-169.
22. Maeda, T.; Inoue, M.; Koshiba, S.; Yabuki, T.; Aoki, M.; Nunokawa, E.; Seki, E.; Matsuda, T.; Motoda, Y.; Kobayashi, A.; et al. Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16). J. Biol. Chem. 2004, 279, 13174-13182.
23. Berman, Z.T.; Moore, L.J.; Knudson, K.E.; Whelan, R.J. Synthesis and structural characterization of the peptide epitope of the ovarian cancer biomarker CA125 (MUC16). Tumour Biol. 2010, 31, 495-502.
24. Bork, P.; Patthy, L. The SEA module: A new extracellular domain associated with O-glycosylation. Protein Sci. 1995, 4, 1421-1425.
25. Julenius, K.; Molgaard, A.; Gupta, R.; Brunak, S. Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites. Glycobiology 2005, 15, 153-164.
26. Apweiler, R.; Bairoch, A.; Wu, C.H.; Barker, W.C.; Boeckmann, B.; Ferro, S.; Gasteiger, E.; Huang, H.; Lopez, R.; Magrane, M.; et al. UniProt: The Universal Protein knowledgebase. Nucleic Acids Res. 2004, 32 (Database issue), D115-D119.
27. Konishi, I.; Fendrick, J.L.; Parmley, T.H.; Quirk, J.G., Jr.; O'Brien, T.J. Epidermal growth factor enhances secretion of the ovarian tumor-associated cancer antigen CA125 from the human amnion WISH cell line. J. Soc. Gynecol. Investig. 1994, 1, 89-96.
28. Lloyd, K.O.; Yin, B.W. Synthesis and secretion of the ovarian cancer antigen CA 125 by the human cancer cell line NIH:OVCAR-3. Tumour Biol. 2001, 22, 77-82.
29. Parry, S.; Silverman, H.S.; McDermott, K.; Willis, A.; Hollingsworth, M.A.; Harris, A. Identification of MUC1 proteolytic cleavage sites in vivo. Biochem. Biophys. Res. Commun. 2001, 283, 715-720.
30. Palmai-Pallag, T.; Khodabukus, N.; Kinarsky, L.; Leir, S.H.; Sherman, S.; Hollingsworth, M.A.; Harris, A. The role of the SEA (sea urchin sperm protein, enterokinase and agrin) module in cleavage of membrane-tethered mucins. FEBS J. 2005, 272, 2901-2911.
31. Nustad, K.; Bast, R.C., Jr.; Brien, T.J.; Nilsson, O.; Seguin, P.; Suresh, M.R.; Saga, T.; Nozawa, S.; Bormer, O.P.; de Bruijn, H.W.; et al. Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen: First report from the ISOBM TD-1 workshop. International Society for Oncodevelopmental Biology and Medicine. Tumour Biol. 1996, 17, 196-219.
32. Nustad, K.; Lebedin, Y.; Lloyd, K.O.; Shigemasa, K.; de Bruijn, H.W.; Jansson, B.; Nilsson, O.; Olsen, K.H.; O'Brien, T.J. Epitopes on CA 125 from cervical mucus and ascites fluid and characterization of six new antibodies. Third report from the ISOBM TD-1 workshop. Tumour Biol. 2002, 23, 303-314.
33. Warren, D.J.; Nustad, K.; Beard, J.B.; O'Brien, T.J. Expression and epitope characterization of a recombinant CA 125 repeat: Fourth report from the ISOBM TD-1 workshop. Tumour Biol. 2009, 30, 51-60.
34. Yin, B.W.; Dnistrian, A.; Lloyd, K.O. Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. Int. J. Cancer 2002, 98, 737-740.
35. Davis, H.M.; Zurawski, V.R., Jr.; Bast, R.C., Jr.; Klug, T.L. Characterization of the CA 125 antigen associated with human epithelial ovarian carcinomas. Cancer Res. 1986, 46 (12 Pt 1), 6143-6148.
36. Halila, H. Detection of ovarian cancer marker CA 125 in human seminal plasma. Tumour Biol. 1985, 6, 207-212.
37. De los Frailes, M.T.; Stark, S.; Jaeger, W.; Hoerauf, A.; Wildt, L. Purification and characterization of the CA 125 tumor-associated antigen from human ascites. Tumour Biol. 1993, 14, 18-29.
38. Bouanene, H.; Miled, A. Conflicting views on the molecular structure of the cancer antigen CA125/MUC16. Dis. Markers 2010, 28, 385-394.
39. Grimwood, J.; Gordon, L.A.; Olsen, A.; Terry, A.; Schmutz, J.; Lamerdin, J.; Hellsten, U.; Goodstein, D.; Couronne, O.; Tran-Gyamfi, M.; et al. The DNA sequence and biology of human chromosome 19. Nature 2004, 428, 529-535.
40. Lloyd, K.O.; Yin, B.W.; Kudryashov, V. Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): Identification as a mucin-type molecule. Int. J. Cancer 1997, 71, 842-850.
41. Weiland, F.; Fritz, K.; Oehler, M.K.; Hoffmann, P. Methods for identification of CA125 from ovarian cancer ascites by high resolution mass spectrometry. Int. J. Mol. Sci. 2012, 13, 9942-9958.
42. Tian, E.; Ten Hagen, K.G. Recent insights into the biological roles of mucin-type O-glycosylation. Glycoconj. J. 2009, 26, 325-334.
43. Hanisch, F.G.; Uhlenbruck, G.; Dienst, C.; Stottrop, M.; Hippauf, E. Ca 125 and Ca 19-9: Two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk. Eur. J. Biochem. 1985, 149, 323-330.
44. Nagata, A.; Hirota, N.; Sakai, T.; Fujimoto, M.; Komoda, T. Molecular nature and possible presence of a membranous glycan-phosphatidylinositol anchor of CA125 antigen. Tumour Biol. 1991, 12, 279-286.
45. Easton, R.L.; Patankar, M.S.; Clark, G.F.; Morris, H.R.; Dell, A. Pregnancy-associated changes in the glycosylation of tamm-horsfall glycoprotein. Expression of sialyl Lewis(x) sequences on core 2 type O-glycans derived from uromodulin. J. Biol. Chem. 2000, 275, 21928-21938.
46. Pastan, I.; Lovelace, E.T.; Gallo, M.G.; Rutherford, A.V.; Magnani, J.L.; Willingham, M.C. Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. Cancer Res. 1991, 51, 3781-3787.
47. Yin, B.W.; Finstad, C.L.; Kitamura, K.; Federici, M.G.; Welshinger, M.; Kudryashov, V.; Hoskins, W.J.; Welt, S.; Lloyd, K.O. Serological and immunochemical analysis of Lewis y (Ley) blood group antigen expression in epithelial ovarian cancer. Int. J. Cancer 1996, 65, 406-412.
48. Jankovic, M.M.; Milutinovic, B.S. Glycoforms of CA125 antigen as a possible cancer marker. Cancer Biomark. 2008, 4, 35-42.
49. Mitic, N.; Milutinovic, B.; Jankovic, M. Assessment of sialic acid diversity in cancer-and non-cancer related CA125 antigen using sialic acid-binding Ig-like lectins (Siglecs). Dis. Markers 2012, 32, 187-194.
50. Bouanene, H.; Saibi, W.; Mokni, M.; Sriha, B.; Ben Fatma, L.; Ben Limem, H.; Ben Ahmed, S.; Gargouri, A.; Miled, A. Biochemical and morphological differences between CA125 isolated from healthy women and patients with epithelial ovarian cancer from Tunisian population. Pathol. Oncol. Res. 2012, 18, 325-330.
51. Jankovic, M.M.; Tapuskovic, B.S. Molecular forms and microheterogeneity of the oligosaccharide chains of pregnancy-associated CA125 antigen. Hum. Reprod. 2005, 20, 2632-2638.
52. Milutinovic, B.; Jankovic, M. Analysis of the protein and glycan partsof CA125 Antigen from human amniotic fluid. Arch. Biol. Sci. Belgrade 2007, 59, 97-103.
53. De Souza, G.A.; Godoy, L.M.; Mann, M. Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors. Genome Biol. 2006, 7, R72.
54. Andersch-Bjorkman, Y.; Thomsson, K.A.; Holmen Larsson, J.M.; Ekerhovd, E.; Hansson, G.C. Large scale identification of proteins, mucins, and their O-glycosylation in the endocervical mucus during the menstrual cycle. Mol. Cell. Proteomics 2007, 6, 708-716.
55. Davies, J.R.; Kirkham, S.; Svitacheva, N.; Thornton, D.J.; Carlstedt, I. MUC16 is produced in tracheal surface epithelium and submucosal glands and is present in secretions from normal human airway and cultured bronchial epithelial cells. Int. J. Biochem. Cell Biol. 2007, 39, 1943-1954.
56. Taylor, C.F.; Paton, N.W.; Lilley, K.S.; Binz, P.A.; Julian, R.K., Jr.; Jones, A.R.; Zhu, W.; Apweiler, R.; Aebersold, R.; Deutsch, E.W.; et al. The minimum information about a proteomics experiment (MIAPE). Nat. Biotechnol. 2007, 25, 887-893.
57. Taylor, C.F.; Binz, P.A.; Aebersold, R.; Affolter, M.; Barkovich, R.; Deutsch, E.W.; Horn, D.M.; Huhmer, A.; Kussmann, M.; Lilley, K.; et al. Guidelines for reporting the use of mass spectrometry in proteomics. Nat. Biotechnol. 2008, 26, 860-861.
58. Binz, P.A.; Barkovich, R.; Beavis, R.C.; Creasy, D.; Horn, D.M.; Julian, R.K., Jr.; Seymour, S.L.; Taylor, C.F.; Vandenbrouck, Y. Guidelines for reporting the use of mass spectrometry informatics in proteomics. Nat. Biotechnol. 2008, 26, 862.
59. States, D.J.; Omenn, G.S.; Blackwell, T.W.; Fermin, D.; Eng, J.; Speicher, D.W.; Hanash, S.M. Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study. Nat. Biotechnol. 2006, 24, 333-338.
60. Schober, Y.; Schramm, T.; Spengler, B.; Rompp, A. Protein identification by accurate mass matrix-assisted laser desorption/ionization imaging of tryptic peptides. Rapid. Commun. Mass Spectrom. 2011, 25, 2475-2483.
61. Ji, Q.C.; Rodila, R.; Gage, E.M.; El-Shourbagy, T.A. A strategy of plasma protein quantitation by selective reaction monitoring of an intact protein. Anal. Chem. 2003, 75, 7008-7014.
62. Chen, Y.; Clark, S.; Wong, T.; Dennis, M.S.; Luis, E.; Zhong, F.; Bheddah, S.; Koeppen, H.; Gogineni, A.; Ross, S.; et al. Armed antibodies targeting the mucin repeats of the ovarian cancer antigen, MUC16, are highly efficacious in animal tumor models. Cancer Res. 2007, 67, 4924-4932.
63. Reinartz, S.; Kohler, S.; Schlebusch, H.; Krista, K.; Giffels, P.; Renke, K.; Huober, J.; Mobus, V.; Kreienberg, R.; DuBois, A.; et al. Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: Immunological response and survival (phase Ib/II). Clin. Cancer Res. 2004, 10, 1580-1587.
64. Leffers, N.; Daemen, T.; Helfrich, W.; Boezen, H.M.; Cohlen, B.J.; Melief, K.; Nijman, H.W. Antigen-specific active immunotherapy for ovarian cancer. Cochrane Database Syst. Rev. 2010, 1, CD007287.
65. Oei, A.L.; Sweep, F.C.; Thomas, C.M.; Boerman, O.C.; Massuger, L.F. The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review). Int. J. Oncol. 2008, 32, 1145-1157.