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.
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References
Putnam FW. Haptoglobin. In: Putman FW, ed.The Plasma Proteins Vol 2, 2nd edn. New York: Academic Press, 1975; 2–50.
Thompson S, Turner GA. Elevated levels of abnormally-fucosylated haptoglobins in cancer sera.Br J Cancer 1987:56; 605–10.
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.
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.
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.
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.
Thompson S, Record CO, Turner GA. Studies of lotus-extracted haptoglobin in inflammatory bowel disease.Biochem Soc Trans 1991:19; 514.
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.
Smets LA, Van Beek WP. Carbohydrate of the tumour cell surface.Biochem Biophys Acta 1984:738; 237–49.
Hakomori S-I. Aberrant glycosylation in tumours and tumour-associated carbohydrate antigens.Adv Cancer Res 1989:52; 257–31.
Turner GA.N-glycosylation of serum proteins in disease and its investigation using lectins.Clin Chim Acta 1992:208; 149–71.
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.
Thompson S, Dargan E, Turner GA. Increased fucosylation and other carbohydrate changes in haptoglobin in ovarian cancer.Cancer Lett. 1992:66: 43–48.
Laurell CB. Electroimmuno assay.Scan J Clin Invest 1972:129; 21–37.
Tasheva B, Dessev G. Artifacts in sodium dodecyl sulfate-polyacrylamide gel electrophoresis due to 2-mercaptoethanol.Anal Biochem 1983:129; 98–102.
Petryniak J, Goldstein IJ. Immunochemical studies on the interaction between synthetic glycoconjugates and α-l-fucosyl binding lectins.Biochemistry 1986:25; 2829–38.
Thompson S, Dargan E, Griffiths ID, Kelly CA, Turner GA. The glycosylation of haptoglobin in rheumatoid arthritis.Clin Chim Acta 1993:220; 107–14.
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.
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.
Brandley BK, Swiedler SJ, Robbins PW. Carbohydrate ligands of the LEC cell adhesion molecules.Cell 1990:63; 861–3.
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.
Jadach J, Turner GA. An ultrasensitive technique for the analysis of glycoprotein using lectin blotting with enhanced chemiluminescence.Anal Biochem 1993:212 293–5.
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Part of this work was published in abstract form,Glycoconjugate J 1993;10; 318.
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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
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DOI: https://doi.org/10.1007/BF00917467