The Carbohydrate on Human Chorionic Gonadotropin Produced by Cancer Cells

  • Laurence A. Cole
  • Robert O. Hussa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 176)


Standard hCG and its subunits in pregnancy urine and serum contain N-linked biantennary oligosaccharides (1), through which they bind the lectin Con A (2). However, as recently shown, that produced by nontrophoblastic malignancies and in vitro by choriocarcinoma cells only partially binds this lectin (Table 1). On this basis, it has been suggested that cancer cell hCG subunits have an alternative oligosaccharide structure (3, 4), or a reduced carbohydrate content or are sugar-free (4). The DoT and CaSki cell lines were established from the tumors of two patients with epidermoid carcinoma of the cervix. Immunoreactive hCG/hCGß was detected in the serum of both patients and in the spent medium from the corresponding cell lines (5, 6). The hCG from DoT and CaSki cell lines only partially binds Con A. To study this phenomenon, the hCG produced by DoT cells was compared with standard hCG in terms of its oligosaccharide structure. Methods are described whereby the oligosaccharides on trace amounts of ectopic glycoprotein can be compared to those of glycoprotein with known oligosaccharide structure. Methods, developed with mg quantities of standard hCGß, were applied to trace amounts of ectopic hCGß from DoT culture fluids.


Human Chorionic Gonadotropin Neuraminic Acid Liquid Scintillation Spectrometry Reductive Methylation Mannose Content 
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  1. 1.
    Kessler, M. J., Reddy, M. S., Shah, R. H., and Bahl, O. P., Structures of N-glycosidic carbohydrate units of human chorionic gonadotropin, J. Biol. Chem. 254:7901 (1979).PubMedGoogle Scholar
  2. 2.
    Baenziger, J. U. and Fiete, D., Structural determinants of concanavalin A specificity for oligosaccharides, J. Biol. Chem. 254:2400 (1979).PubMedGoogle Scholar
  3. 3.
    Cox, G. S., Glycosylation of the chorionic gonadotropin alpha subunit synthesized by HeLa cells, Cancer Res. 41:3087 (1981).PubMedGoogle Scholar
  4. 4.
    Yoshimoto, Y., Wolfsen, A., and Odell, W. D., Glycosylation, a variable in the production of hCG by cancers, Amer. J. Med. 67:414 (1979).PubMedCrossRefGoogle Scholar
  5. 5.
    Pattillo, R. A., Hussa, R. O., Story, M. T., Ruckert, A. C. F., Shalaby, M. R., and Mattingly, R. F., Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line, Science 196:1456 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    Hussa, R. O., Pattillo, R. A., Ruckert, A. C. F., and Scheuermann, K. W., Effects of butyrate and dibutyryl cyclic AMP on hCG-secreting trophoblastic and non-trophoblastic cells, J. Clin. Endocrinol. Metab.. 46:69 (1978).PubMedCrossRefGoogle Scholar
  7. 7.
    Braunstein, G. D., Kamdar, V., Rasor, J., Swaminathan, N., and Wade, M. E., Widespread distribution of chorionic gonadotropinlike substance in normal human tissues, J. Clin. Endocrinol. Metab.. 49:917 (1979).PubMedCrossRefGoogle Scholar
  8. 8.
    Cole, L. A. and Hussa, R. O., Use of glycosidase digested human chorionic gonadotropin 8-subunit to explain the partial binding of ectopic glycoprotein hormones to Con A, Endocrinology 109: 2276 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    Cole, L. A., Hussa, R. O., and Rao, C. V., Discordant synthesis and secretion of human chorionic gonadotropin and subunits by cervical carcinoma cells, Cancer Res. 41:1615 (1981).PubMedGoogle Scholar
  10. 10.
    Cassidy, J., Jourdian, G. W., and Roseman, S., Sialidase from Clostridium perfringens, Methods Enzymol.. 8:680 (1966).CrossRefGoogle Scholar
  11. 11.
    Li, Y. and Li, S., Studies on the glycosidases in Jack bean meal, J. Biol. Chem.. 243:3994 (1968).PubMedGoogle Scholar
  12. 12.
    Tarentino, A. and Maley, R., A comparison of the substrate specificities of endo-B-N-acetylglucosaminidases from Streptomyces griseus and Diplococcus pneumonae, Biochem. Biophys. Res. Commun.. 253:455 (1975).CrossRefGoogle Scholar
  13. 13.
    Bahl, O. P. and Agrawal, K. M. L., Glycosidases of Aspergillus niger, J. Biol. Chem.. 244:2970 (1969).PubMedGoogle Scholar
  14. 14.
    Warren, L., The thiobarbituric acid assay of sialic acids, J. Biol. Chem.. 234:1971 (1959).PubMedGoogle Scholar
  15. 15.
    Schachter, J., Enzymic microassays for D-mannose, D-glucose, D-galactose, L-fucose, and D-glucosamine, Methods Enzymol.. 41:3 (1975).PubMedCrossRefGoogle Scholar
  16. 16.
    Wallensfell, K. and Kurz, G., 8-D-Galactose dehydrogenase from Pseudomonas saccharophilia, Methods Enzymol.. 4:112 (1964).Google Scholar
  17. 17.
    Ressig, J. L., Stominger, J. L., and Leloir, L. E., A modified colorimetric method for the estimation of N-acetylamino sugars, J. Biol. Chem.. 217:959 (1955).Google Scholar
  18. 18.
    Davidson, E. A., Analysis of sugars found on mucopolysaccharides, Methods Enzymol.. 8:52 (1966).CrossRefGoogle Scholar
  19. 19.
    Narasimhan, S., Wilson, J. R., Martin, E., and Schachter, H., Structural basis for four distinct elution profiles on concanavalin A-Sepharose affinity chromatography of glycopeptides, Can. J. Biochem.. 57:83 (1979).PubMedGoogle Scholar
  20. 20.
    Baenziger, J. U. and Fiete, D., Structural determinants of Ricinus communis agglutinin and toxin specificity for oligosaccharides, J. Biol. Chem.. 254:7975 (1979).Google Scholar
  21. 21.
    Goldstein, I. J. and Hayes, C. E., Lectins: carbohydrate binding proteins, Adv. Carbohydrate Chem. Biochem.. 35:127 (1978).CrossRefGoogle Scholar
  22. 22.
    Cole, L. A., Birken, S., Sutphen, S., Hussa, R. O., and Pattillo, R. A., Absence of the COOH-terminal peptide on ectopie human chorionic gonadotropin ß-subunit (hCGß), Endocrinology 110:2198 (1982).PubMedCrossRefGoogle Scholar
  23. 23.
    Hussa, R. O., Immunologic and physical characterization of hCG and its subunits in cultures of human malignant trophoblast, J. Clin. Endocrinol. Metab.. 44:1154 (1977).PubMedCrossRefGoogle Scholar
  24. 24.
    Miyachi, Y., Vaitukaitis, J. L., Nieschlag, E., and Lipsett, M. B., Enzymatic radioiodination of gonadotropins, J. Clin.. Endocrinol. Metab.. 34:23 (1972).PubMedCrossRefGoogle Scholar
  25. 25.
    Rodbard, D., Statistical quality control and routine data processing for radioimmunoassays and immunoradiometric assays, Clin. Chem.. 20:1255 (1974).PubMedGoogle Scholar
  26. 26.
    Tack, B. F., Dean, J., Eilat, D., Lorenz, P. E., and Schechter, A. N., Tritium labeling of proteins to high specific activity by reductive methylation, J. Biol. Chem.. 255:8842 (1980).PubMedGoogle Scholar
  27. 27.
    Story, M. T., Cole, L. A., and Hussa, R. O., A procedure using immobilized antibody for the isolation of the 13-subunit of human chorionic gonadotropin from the culture fluid of a ßsubuni’t-secreting nontrophoblastic cell line, J. Clin. Endocrinol. Metab.. 53:1090 (1981).PubMedCrossRefGoogle Scholar
  28. 28.
    Kessler, M. J., Mise, T., Ghai, R. D., and Bahl, O. P., Structure and location of the O-glycosidic carbohydrate units of human chorionic gonadotropin, J. Biol. Chem.. 254:7909 (1979).PubMedGoogle Scholar
  29. 29.
    Endo, Y., Yamashita, K., Tachibana, Y., Tojo, S., and Kobata, A., Structure of the asparagine-linked sugar chains of human chorionic gonadotropin, J. Biochem.. 85:669 (1979).PubMedGoogle Scholar
  30. 30.
    Baenziger, J. U. and Fiete, D., Structure of the complex oligosaccharides of fetuin, J. Biol. Chem.. 254:789 (1979).PubMedGoogle Scholar
  31. 31.
    Muramatsu, T., Endo-ß-N-acetylglucosaminidase D from Diplococcus pneumoniae, Methods Enzymol.. 50:555 (1978).PubMedCrossRefGoogle Scholar
  32. 32.
    Atkinson, P. H. and Hakimi, J., Alterations in glycoproteins of the cell surface, in: “The Biochemistry of Glycoproteins and Proteoglycans,” W. J. Lennarz, ed., Plenum Press, New York (1980), p. 191.CrossRefGoogle Scholar
  33. 33.
    Kornfeld, R. and Kornfeld, S., Structure of glycoproteins and their oligosaccharide units, in: “The Biochemistry of Glycoproteins and Proteoglycans,” W. J. Lennarz, ed., Plenum Press, New York (1980), p. 1.CrossRefGoogle Scholar
  34. 34.
    Irimura, T., Tsuji, T., Tagami, S., Yamamoto, K., and Osawa, T., Structure of a complex-type sugar chain of human glycophorin A., Biochemistry 20:560 (1981).PubMedCrossRefGoogle Scholar
  35. 35.
    Harpaz, N. and Schachter, H., Control of glycoprotein synthe-sis, J. Biol. Chem.. 255:4894 (1980).PubMedGoogle Scholar
  36. 36.
    Narasimhan, S., Harpaz, N., Longmore, G., Carver, J. P., Grey, A. A., and Schachter, H., Control of glycoprotein synthesis, J. Biol. Chem.. 255:4876 (1980).PubMedGoogle Scholar
  37. 37.
    Baenziger, J. U. and Kornfeld, S., Structure of the carbohydrate units of IgA immunoglobulin, J. Biol. Chem.. 249: 7260 (1974).PubMedGoogle Scholar
  38. 38.
    Yamashita, K., Tachibana, Y., and Kobata, A., The structure of the galactose-containing sugar chains of ovalbumin, J. Biol. Chem. 253:3862 (1978).PubMedGoogle Scholar
  39. 39.
    Fournet, B., Montrevil, J., Strecker, G., Dorland, L., Haverkamp, J., Vliegenthart, J., Binette, P., and Schmid, K., Determination of the structures of 16 asialo-carbohydrate units derived from human plasma al-acid glycoprotein by 360 MHz 1H NMR spectroscopy and permethylation analysis, Biochemistry 17:5206 (1978).PubMedCrossRefGoogle Scholar
  40. 40.
    Yamashita, K., Liang, C-J., Funakoshi, S., and Kobata, A., Structural studies of asparagine-linked sugar chains of human ceruloplasmin, J. Biol. Chem.. 256:1283 (1981).PubMedGoogle Scholar
  41. 41.
    Mega, T., Lujan, E., and Yoshida, A., Studies on the oligosaccharide chains of human a1-protease inhibitor, J. Biol. Chem.. 255:4057 (1980).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Laurence A. Cole
    • 1
  • Robert O. Hussa
    • 2
  1. 1.Department of PharmacologyUniversity of MichiganAnn ArborUSA
  2. 2.Department of Gynecology & ObstetricsMedical College of WisconsinMilwaukeeUSA

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