Skip to main content

Advertisement

Log in

Changes in the fucose content of haptoglobin in breast and ovarian cancer: Association with disease progression

  • Research Papers
  • Published:
Glycosylation & Disease

Abstract

There is increasing evidence for changes in fucosylation in cancer. Previously, we showed that the fucose-specific lectin,Lotus tetragonolobus, extracts an abnormal form of haptoglobin (Hp) from cancer sera. This study investigates the monosaccharide content of Hp obtained from women with ovarian and breast cancer at different stages of their disease. In both cancers, Hp fucose was low when the disease was benign or in remission and much higher when the disease was progressive. This occurred whether the data was expressed per mole of protein or per three mannose residues. Changes in other monosaccharides were minor compared with fucose. There were small increases in theN-acetylglucosamine and galactose content (per three mannoses) in ovarian cancer, suggesting that some glycan chains have increased branching. The latter was independent of disease activity which may be due to some indirect cause such as cytotoxic therapy or an inflammatory response. When ovarian cancer patients were in remission, the number of glycosylation sites on Hp was reduced. Hp isolated from patients with early, but not advanced breast cancer also appeared to have increased glycan branching. The increased fucosylated Hp may interfere with fucose-mediated adhesion reactions of cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Putnam FW. Haptoglobin. In: Putman FW, ed.The Plasma Proteins Vol 2, 2nd edn. New York: Academic Press, 1975; 2–50.

    Google Scholar 

  2. Thompson S, Turner GA. Elevated levels of abnormally-fucosylated haptoglobins in cancer sera.Br J Cancer 1987:56; 605–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Thompson S, Cantwell BMJ, Cornell C, Turner GA. Abnormally-fucosylated haptoglobin: a cancer marker for tumour burden but not gross liver metastasis.Br J Cancer 1991:64; 386–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Thompson S, Cantwell BMJ, Matta KL, Turner GA. Parallel changes in the blood levels of abnormally-fucosylated haptoglobin and alpha 1,3 fucosyltransferases in relationship to tumour burden: more evidence for a disturbance of fucose metabolism in cancer.Cancer Lett. 1992:65; 115–21.

    Article  CAS  PubMed  Google Scholar 

  5. Thompson S, Kelly CA, Griffiths ID, Turner GA. Abnormally-fucosylated serum haptoglobins in patients with inflammatory joint disease.Clin Chim Acta 1989:184; 251–8.

    Article  CAS  PubMed  Google Scholar 

  6. Chambers W, Thompson S, Skillen AW, Record CO, Turner GA. Abnormally fucosylated haptoglobin as a marker for alcoholic liver disease but not excessive alcohol consumption or non-alcoholic liver disease.Clin Chim Acta 1993:219; 177–82.

    Article  CAS  PubMed  Google Scholar 

  7. Thompson S, Record CO, Turner GA. Studies of lotus-extracted haptoglobin in inflammatory bowel disease.Biochem Soc Trans 1991:19; 514.

    Google Scholar 

  8. Nilsson B, Lowe M, Osada J, Ashwell G, Zopf D. The carbohydrate structure of human haptoglobin 1-1 In: Yamakawa T, et al. eds.Glycoconjugates. Proc. 6th In. Symp. on Glyconjugates, pp. 275. Tokyo: Japan Scientific Societies Press, 1981.

    Google Scholar 

  9. Smets LA, Van Beek WP. Carbohydrate of the tumour cell surface.Biochem Biophys Acta 1984:738; 237–49.

    CAS  PubMed  Google Scholar 

  10. Hakomori S-I. Aberrant glycosylation in tumours and tumour-associated carbohydrate antigens.Adv Cancer Res 1989:52; 257–31.

    Article  CAS  PubMed  Google Scholar 

  11. Turner GA.N-glycosylation of serum proteins in disease and its investigation using lectins.Clin Chim Acta 1992:208; 149–71.

    Article  CAS  PubMed  Google Scholar 

  12. Takada A, Ohmori K, Yoneda T, et al. Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium.Cancer Res 1993:53; 354–61.

    CAS  PubMed  Google Scholar 

  13. Thompson S, Dargan E, Turner GA. Increased fucosylation and other carbohydrate changes in haptoglobin in ovarian cancer.Cancer Lett. 1992:66: 43–48.

    Article  CAS  PubMed  Google Scholar 

  14. Laurell CB. Electroimmuno assay.Scan J Clin Invest 1972:129; 21–37.

    Article  Google Scholar 

  15. Tasheva B, Dessev G. Artifacts in sodium dodecyl sulfate-polyacrylamide gel electrophoresis due to 2-mercaptoethanol.Anal Biochem 1983:129; 98–102.

    Article  CAS  PubMed  Google Scholar 

  16. Petryniak J, Goldstein IJ. Immunochemical studies on the interaction between synthetic glycoconjugates and α-l-fucosyl binding lectins.Biochemistry 1986:25; 2829–38.

    Article  CAS  PubMed  Google Scholar 

  17. Thompson S, Dargan E, Griffiths ID, Kelly CA, Turner GA. The glycosylation of haptoglobin in rheumatoid arthritis.Clin Chim Acta 1993:220; 107–14.

    Article  CAS  PubMed  Google Scholar 

  18. Mann AC, Record CO, Self CH, Turner GA. Monosaccharide composition of haptoglobin in liver diseases and alcohol abuse: large changes in glycosylation associated with alcoholic liver disease.Clin Chim Acta 1994: in press.

  19. van Dijk W, Turner GA, Mackiewicz A. Changes in glycosylation of acute-phase proteins in health and disease: occurrence, regulation and function.Glycosylation Disease 1994:1; 5–14.

    Article  CAS  Google Scholar 

  20. Brandley BK, Swiedler SJ, Robbins PW. Carbohydrate ligands of the LEC cell adhesion molecules.Cell 1990:63; 861–3.

    Article  CAS  PubMed  Google Scholar 

  21. van der Linden ECM, De Graff TW, Anbergen MG, et al. Preparative affinity electrophoresis of different glycoforms of serum glycoproteins: application for the study of inflammation induced expression of sialyl-Lewisx groups on α1 acid glycoprotein (orosomucoid).Glycosylation Disease 1994:1; 45–52.

    Article  Google Scholar 

  22. Jadach J, Turner GA. An ultrasensitive technique for the analysis of glycoprotein using lectin blotting with enhanced chemiluminescence.Anal Biochem 1993:212 293–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Part of this work was published in abstract form,Glycoconjugate J 1993;10; 318.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dargan, E., Thompson, S., Cantwell, B.M.J. et al. Changes in the fucose content of haptoglobin in breast and ovarian cancer: Association with disease progression. Glycosylation & Disease 1, 37–43 (1994). https://doi.org/10.1007/BF00917467

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00917467

Key words

Navigation