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Glycosylation of alpha-1-proteinase inhibitor and haptoglobin in ovarian cancer: evidence for two different mechanisms

  • Glycosylation & Disease Section Special Issue — Blood Glycoconjugates As Markers Of Disease
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Abstract

The change in glycosylation of the two acute-phase proteins, alpha-1-proteinase inhibitor (API) and haptoglobin (Hp), in progressive ovarian cancer is different. This has been shown by monosaccharide analysis and lectin-binding studies of proteins purified from serum. In the glycan chains of API, there is decreased branching (more biantennary chains), less branches ending in alpha 2-3 sialic acid, more branches ending in alpha 2-6 sialic acid and more fucose, probably linked alpha 1-6 to the core region. On the other hand, Hp shows increased branching (more triantennary chains), more branches ending in alpha 2-3 sialic acid, less branches ending in alpha 2-6 sialic acid, and more fucose, probably in the alpha 1-3 linkage at the end of the chains. This is surprising because API and Hp are thought to be glycosylated by a common pathway in the liver. We have also shown that the fucose-specific lectin,lotus tetragonolobus, extracts abnormal forms of both Hp and API in ovarian cancer, but the expression of this Hp is related to tumour burden and the expression of this API is related to lack of response to therapy. It is suggested that this difference in the behaviour of API and Hp in ovarian cancer may be associated with the different changes in their glycosylation. Of the many mechanisms that could explain these findings, a likely one is that a pathological process is removing API with triantennary chains from the circulation. In addition to their normal roles (API-enzyme inhibitor and Hp-transport protein) these proteins are reported to have many other effects in biological systems, such as immunosuppression. As correct glycosylation of API and Hp is required for their normal stability/activity, changes in glycosylation could affect their functions in ovarian cancer and these modifications could alter the course of the disease.

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References

  1. Turner GA (1995) In:EQAS '94 Proceedings (in press).

  2. Turner GA (1992)Clin Chim Acta 208:149–71.

    Google Scholar 

  3. Thompson S, Guthrie D, Turner GA (1988)Br J Cancer 58:589–93.

    Google Scholar 

  4. Thompson S, Wong E, Cantwell BMJ, Turner GA (1990)Clin Chim Acta 19313–26.

    Google Scholar 

  5. Goodarzi MT, Turner GA (1995)Clin Chim Acta (in press).

  6. Thomson S, Turner GA (1987)Br J Cancer 56:605–10.

    Google Scholar 

  7. Thomson S, Cantwell BMJ, Cornell C, Turner GA (1991)Br J Cancer 64:386–90.

    Google Scholar 

  8. Thompson S, Dargan E, Turner GA (1992)Cancer Lett 66:43–48.

    Google Scholar 

  9. Dargan E, Thompson S, Cantwell BMJ, Wilson RG, Turner GA (1994)Glycosyl & Dis 1:37–43.

    Google Scholar 

  10. Gordon AH, Koj A (1985)Research Monographs in Cell and Tissue Physiology, vol 10. Netherlands: Elsevier Science Publishers BV.

    Google Scholar 

  11. Carrell RW (1986)Clin Invest 77:1427–31.

    Google Scholar 

  12. Dobryszycka W (1993) In: Mackiewicz A, Kushner I, Baumann H, eds. Acute phase proteins: molecular biology, biochemistry, and clinical applications. Boca Raton: CRC Press, 1993;185–206.

    Google Scholar 

  13. Perlmutter DH (1993) In:Acute Phase Proteins: Molecular Biology, Biochemistry, and Clinical Applications, (Mackiewicz A, Kushner I, Baumann H, eds) pp. 150–67, Boca Raton: CRC Press.

    Google Scholar 

  14. Kushner I, Mackiewicz A (1993) In:Acute Phase Proteins: Molecular Biology, Biochemistry, and Clinical Applications, (Mackiewicz A, Kushner I, Baumann H, eds) pp. 3–19, Boca Raton: CRC Press.

    Google Scholar 

  15. Turner GA, Skillen AW, Baumah P, Guthrie D, Welsh J, Harrison J, Kowalski A (1985)J Clin Path 38:588–92.

    Google Scholar 

  16. Hodges LC, Laine R, Chan SK (1979)J Biol Chem 254:8208–12.

    Google Scholar 

  17. Mega T, Lujane E, Yoshida A (1980)J Biol Chem 255:4057–61.

    Google Scholar 

  18. Saitoh A, Aoyagi Y, Asakura H (1993)Arch Biochem Biophys 303:281–87.

    Google Scholar 

  19. Chan SK, Luby J, Wu YC (1973)FEBS Lett 35:79–83.

    Google Scholar 

  20. Bayard B, Kerkaert JP, Laine A, Hayem A (1982)Eur J Biochem 124:371–76.

    Google Scholar 

  21. Nilsson B, Lowe M, Osada J, Ashwell G, Zopf D (1981) In:Glycoconjugates Proc 6th Int Sym Glyco Tokyo: Japan Scientific Societies Press. (Yamakawa T, Osawa T, Handa F, eds) pp. 275–76.

  22. Katnik I, Jadach J, Krotkiewski H, Gerber J (1994)Glycosyl & Dis 2:97–104.

    Google Scholar 

  23. Goodarzi T, Rafiq M, Turner GA (1995)Biochem Soc Trans 23:168S.

    Google Scholar 

  24. De Vries T, van Den Eijnden DH (1992)Histochem J 24:761–70.

    Google Scholar 

  25. Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H (1987)Proc Natl Acad Sci USA 84:7251–55.

    Google Scholar 

  26. Baumann H, Richards C, Gauldie J (1987)J Immunol 139:4122–28.

    Google Scholar 

  27. Pos O, van Dijk W, Ladiges N, Linthorst C, Sela M, van Tiel D, Boers W (1988)Eur J Cell Biol 46:121–28.

    Google Scholar 

  28. Mackiewicz A, Kushner I (1989)Scand J Immunol 29:265–71.

    Google Scholar 

  29. Mackiewicz A, Kushner I (1990)Inflammation 14:485–97.

    Google Scholar 

  30. Mackiewicz A, Pos O, van der Stelt M, Yap SH, Kapcinska M, Kaciak M, Dewey MJ, Berger FG, Baumann H, Kushner I, van Dijk W (1992) In:Affinity Electrophoresis: Principles and Application (Breborowicz J, Mackiewicz A, eds) pp. 135–53. Boca Raton: CRC Press.

    Google Scholar 

  31. van Dijk W, Turner GA, Mackiewicz A (1994)Glycosyl & Disease 1:5–14.

    Google Scholar 

  32. Rademacher TW, Parekh RB, Dwek RA (1988)Ann Rev Biochem 57:785–838.

    Google Scholar 

  33. Oh S-K, Very DL, Ettinger R, Walker J, Giampaolo C, Bernado J (1989)Hybridoma 8:449.

    Google Scholar 

  34. Shurbaji MS, Pasternack GR, Kuhajda FP (1991)Am J Clin Path 96:238–42.

    Google Scholar 

  35. Shurbaji MS, Thurmond TS, Pasternack GR, Kuhajda FP (1991)Lab Invest 64:A52.

    Google Scholar 

  36. Redston MS, Kern SE, Vogelstein B, Hamilton SR (1992)Lab Invest 66:A47.

    Google Scholar 

  37. Schachter H (1991)Glycobiology 1:453–61.

    Google Scholar 

  38. Koj A (1974)Structure and Function of Plasma Proteins vol 1 (Allison AC, ed.) pp. 73–120. London: Plenum Press.

    Google Scholar 

  39. Cooper EH, Stone J (1979) Acute-phase reactant proteins in cancer.Adv Cancer Res 30:1–44.

    Google Scholar 

  40. Parivar K, Tolentino L, Taylor G, Oie S (1992)J Pharm Pharmacology 44:447–50.

    Google Scholar 

  41. Laurell C-B, Jeppsson J-O (1975) In:The Plasma Proteins vol 1 2nd edition (Putnam FW, ed) pp. 229–264. New York: Academic Press.

    Google Scholar 

  42. Bleasby AJ, Knowles JC, Cooper EH (1986)Int J React VIII:393–400.

    Google Scholar 

  43. Tahara E, Itoh H, Taniyama K, Yokoyaki H, Hata J (1984)Human Path 15:957–64.

    Google Scholar 

  44. Guzdek A, Potempa J, Dubin A, Travis J (1990)FEBS Lett 72:125–27.

    Google Scholar 

  45. Powell LM, Pain R (1992)J Mol Biol 2224:241–52.

    Google Scholar 

  46. Putnam FW (1984) In:The Plasma Proteins. Structure, Function and Genetic Control, vol IV (Putnum FW, ed) pp. 45–166. London: Academic Press.

    Google Scholar 

  47. Cox DW (1975)Am J Hum Gen 27:165–77.

    Google Scholar 

  48. Carlson J, Ariksson S, Alm R, Kjellstrom T (1984)Hepatology 4:235–41.

    Google Scholar 

  49. Kaartinen V, Mononen I (1988)Biochim Biophys Acta 953:345–52.

    Google Scholar 

  50. Katnik I (1984)Biochim Biophsy Acta 790:8–14.

    Google Scholar 

  51. Baskies AM, Chretien PB, Weiss JF, Makich RW, Beveridge RA, Catalona WJ, Spiegel HE (1980)Cancer 45:3050–60.

    Google Scholar 

  52. Okumura Y, Kudo J, Ikuta T, Kurokawa S, Ishibashi H, Okubo H (1985)Inflammation 9:211–19.

    Google Scholar 

  53. Lejeune P-J, Mallet B, Farnarier C, Kaplanski S (1989)Biochim Biophys Acta 990:122–27.

    Google Scholar 

  54. Aoshiba K, Natashi A, Ishihara Y, Kagawa J, Takizawa T (1993)J Clin Lab Med 122:333–40.

    Google Scholar 

  55. Shasby M (1989)Am Rev Resp Dis 1:451–53.

    Google Scholar 

  56. Smith CW, Hollers JC, Patrick RA, Hassett C (1979)J Clin Invest 63:221–29.

    Google Scholar 

  57. Samak R, Edelstein R, Israel L (1982)Cancer Immunol Immunother 38:38–43.

    Google Scholar 

  58. Baseler MW, Burrel R (1983)Inflammation 7:387–400.

    Google Scholar 

  59. Beisembaeva RU, Mursagalieva AT, Dzhumalieva, Shaikenova TE, Mevkh AT (1990)FEBS Lett 269:125–27.

    Google Scholar 

  60. Frohlander N, Ljunggren O, Lerner UH (1991)Biochem Biophys Res Comm 178:343–51.

    Google Scholar 

  61. Oh S-K, Pavlotsky N, Tauber AI (1990)J Leukocye Biol 47:142–48.

    Google Scholar 

  62. Brandley BK, Swiedler SJ, Robbins PW (1990)Cell 63:861–63.

    Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Clinical Biochemistry, The Medical School, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK

    G. A. Turner, M. T. Goodarzi & S. Thompson

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  1. G. A. Turner
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  2. M. T. Goodarzi
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  3. S. Thompson
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Turner, G.A., Goodarzi, M.T. & Thompson, S. Glycosylation of alpha-1-proteinase inhibitor and haptoglobin in ovarian cancer: evidence for two different mechanisms. Glycoconjugate J 12, 211–218 (1995). https://doi.org/10.1007/BF00731322

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