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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Dec;71(12):4869–4873. doi: 10.1073/pnas.71.12.4869

Alterations of Membrane Glycopeptides in Human Colonic Adenocarcinoma

Young S Kim 1,2, Richard Isaacs 1,2, Jose M Perdomo 1,2
PMCID: PMC434000  PMID: 4140512

Abstract

Membrane glycopeptides were examined in human colonic adenocarcinoma and normal colonic mucosa. The carbohydrates of membrane glycopeptides were found to be markedly reduced in tumor tissue and the relative proportions of the various sugars were altered. Although all of the sugars were lower in tumor tissue when compared to the adjacent normal mucosa, galactosamine, fucose, and sialic acid were more significantly reduced. Examination of the blood group activity and lectin-binding properties of membrane glycopeptides revealed that specific carbohydrate structures had changed in the tumor tissue. Most striking of these changes was the disappearance of glycoprotein-associated blood group A activity. Assay of the enzyme responsible for synthesis of the blood group A determinant showed that this glycosyltransferase activity was greatly diminished in tumor tissue. A galactosyltransferase and a fucosyltransferase were also significantly lower in the tumor tissue whereas the levels of another galactosyltransferase and a sialyltransferase were unaltered. Glycosidase activities in the normal and tumor tissues were similar. The results show that an alteration in glycoprotein biosynthesis occurred during tumorigenesis that resulted in a modified membrane glycoprotein composition and that these changes are probably a reflection of reduced levels of the enzymes responsible for glycoprotein synthesis.

Keywords: lectins, glycosyltransferases, glycosidases

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AMINOFF D. Methods for the quantitative estimation of N-acetylneuraminic acid and their application to hydrolysates of sialomucoids. Biochem J. 1961 Nov;81:384–392. doi: 10.1042/bj0810384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agrawal B. B., Goldstein I. J. Physical and chemical characterization of concanavalin A, the hemagglutinin from jack bean (Canavalia ensiformis). Biochim Biophys Acta. 1967 Feb 21;133(2):376–379. doi: 10.1016/0005-2795(67)90081-5. [DOI] [PubMed] [Google Scholar]
  3. Bella A. M., Jr, Kim Y. S. An improved method of separating glucosaminitol from galactosaminitol and their amino sugars on an amino acid analyzer. J Chromatogr. 1970 Sep 16;51(2):314–315. doi: 10.1016/s0021-9673(01)96872-4. [DOI] [PubMed] [Google Scholar]
  4. Bella A., Jr, Kim Y. S. Biosynthesis of intestinal glycoprotein: a study of an (1 lead to 2) fucosyltransferase in rat small intestinal mucosa. Arch Biochem Biophys. 1971 Dec;147(2):753–761. doi: 10.1016/0003-9861(71)90435-8. [DOI] [PubMed] [Google Scholar]
  5. Bosmann H. B., Pike G. Z. Glycoprotein synthesis and degradation: glycoprotein: N-acetyl glucosamine transferase, proteolyticand glycosidase activity in normal and polyoma virus transformeBHK cells. Life Sci II. 1970 Dec 22;9(24):1433–1440. doi: 10.1016/0024-3205(70)90104-9. [DOI] [PubMed] [Google Scholar]
  6. Buck C. A., Fuhrer J. P., Soslau G., Warren L. Membrane glycopeptides from subcellular fractions of control and virus-transformed cells. J Biol Chem. 1974 Mar 10;249(5):1541–1550. [PubMed] [Google Scholar]
  7. Buck C. A., Glick M. C., Warren L. A comparative study of glycoproteins from the surface of control and Rous sarcoma virus transformed hamster cells. Biochemistry. 1970 Nov 10;9(23):4567–4576. doi: 10.1021/bi00825a016. [DOI] [PubMed] [Google Scholar]
  8. Cumar F. A., Brady R. O., Kolodny E. H., McFarland V. W., Mora P. T. Enzymatic block in the synthesis of gangliosides in DNA virus-transformed tumorigenic mouse cell lines. Proc Natl Acad Sci U S A. 1970 Oct;67(2):757–764. doi: 10.1073/pnas.67.2.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davidsohn I., Kovarik S., Lee C. L. A, B, and O substances in gastrointestinal carcinoma. Arch Pathol. 1966 May;81(5):381–390. [PubMed] [Google Scholar]
  10. Fishman P. H., Brady R. O., Bradley R. M., Aaronson S. A., Todaro G. J. Absence of a specific ganglioside galactosyltransferase in mouse cells transformed by murine sarcoma virus. Proc Natl Acad Sci U S A. 1974 Feb;71(2):298–301. doi: 10.1073/pnas.71.2.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gahmberg C. G., Hakomori S. I. Altered growth behavior of malignant cells associated with changes in externally labeled glycoprotein and glycolipid. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3329–3333. doi: 10.1073/pnas.70.12.3329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Glick M. C., Kimhi Y., Littauer U. Z. Glycopeptides from surface membranes of neuroblastoma cells. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1682–1687. doi: 10.1073/pnas.70.6.1682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grimes W. J. Sialic acid transferases and sialic acid levels in normal and transformed cells. Biochemistry. 1970 Dec 22;9(26):5083–5092. doi: 10.1021/bi00828a007. [DOI] [PubMed] [Google Scholar]
  14. Hakomori S. I., Koscielak J., Bloch K. J., Jeanloz R. W. Immunologic relationship between blood group substances and a fucose-containing glycolipid of human adenocarcinoma. J Immunol. 1967 Jan;98(1):31–38. [PubMed] [Google Scholar]
  15. Hakomori S. I., Murakami W. T. Glycolipids of hamster fibroblasts and derived malignant-transformed cell lines. Proc Natl Acad Sci U S A. 1968 Jan;59(1):254–261. doi: 10.1073/pnas.59.1.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hakomori S. Cell density-dependent changes of glycolipid concentrations in fibroblasts, and loss of this response in virus-transformed cells. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1741–1747. doi: 10.1073/pnas.67.4.1741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ito S. The enteric surface coat on cat intestinal microvilli. J Cell Biol. 1965 Dec;27(3):475–491. doi: 10.1083/jcb.27.3.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Keenan T. W., Morré D. J. Mammary carcinoma: enzymatic block in disialoganglioside biosynthesis. Science. 1973 Nov 20;182(4115):935–937. doi: 10.1126/science.182.4115.935. [DOI] [PubMed] [Google Scholar]
  19. Kim J. H., Shome B., Liao T. H., Pierce J. G. Analysis of neutral sugars by gas-liquid chromatography of alditol acetates: application to thyrotropic hormone and other glycoproteins. Anal Biochem. 1967 Aug;20(2):258–274. doi: 10.1016/0003-2697(67)90031-0. [DOI] [PubMed] [Google Scholar]
  20. Kim Y. S., Birtwhistle W., Kim Y. W. Peptide hydrolases in the bruch border and soluble fractions of small intestinal mucosa of rat and man. J Clin Invest. 1972 Jun;51(6):1419–1430. doi: 10.1172/JCI106938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kim Y. S., Perdomo J. M. Membrane glycoproteins of the rat small intestine. Chemical composition of membrane glycoproteins. Biochim Biophys Acta. 1974 Mar 14;342(1):111–124. doi: 10.1016/0005-2795(74)90112-3. [DOI] [PubMed] [Google Scholar]
  22. Kim Y. S., Perdomo J., Bella A., Jr, Nordberg J. N-acetyl-D-galactosaminyltransferase in human serum and erythrocyte membranes. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1753–1756. doi: 10.1073/pnas.68.8.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kim Y. S., Perdomo J. Glycoprotein biosynthesis in small intestine. 3. Enzymatic basis for the difference in the antigenicity of mucins. J Clin Invest. 1972 May;51(5):1135–1145. doi: 10.1172/JCI106906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kim Y. S., Perdomo J., Nordberg J. Glycoprortein biosynthesis in small intestinal mucosa. I. A study of glycosyltransferases in microsomal subfractions. J Biol Chem. 1971 Sep 10;246(17):5466–5476. [PubMed] [Google Scholar]
  25. Kim Y. S., Perdomo J., Whitehead J. S., Curtis K. J. Glycosyltransferases in human blood. II. Study of serum galactosyltransferase and N-acetylgalactosaminyltransferase in patients with liver diseases. J Clin Invest. 1972 Aug;51(8):2033–2039. doi: 10.1172/JCI107009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Klenk H. D., Choppin P. W. Glycosphingolipids of plasma membranes of cultured cells and an enveloped virus (SV5) grown in these cells. Proc Natl Acad Sci U S A. 1970 May;66(1):57–64. doi: 10.1073/pnas.66.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kobata A., Grollman E. F., Ginsburg V. An enzymic basis for blood type A in humans. Arch Biochem Biophys. 1968 Mar 20;124(1):609–612. doi: 10.1016/0003-9861(68)90373-1. [DOI] [PubMed] [Google Scholar]
  28. Marchesi V. T., Tillack T. W., Jackson R. L., Segrest J. P., Scott R. E. Chemical characterization and surface orientation of the major glycoprotein of the human erythrocyte membrane. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1445–1449. doi: 10.1073/pnas.69.6.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Meezan E., Wu H. C., Black P. H., Robbins P. W. Comparative studies on the carbohydrate-containing membrane components of normal and virus-transformed mouse fibroblasts. II. Separation of glycoproteins and glycopeptides by sephadex chromatography. Biochemistry. 1969 Jun;8(6):2518–2524. doi: 10.1021/bi00834a039. [DOI] [PubMed] [Google Scholar]
  30. Mora P. T., Fishman P. H., Bassin R. H., Brady R. O., McFarland V. W. Transformation of Swiss 3T3 cells by murine sarcoma virus is followed by decrease in a glycolipid glycosyltransferase. Nat New Biol. 1973 Oct 24;245(147):226–229. doi: 10.1038/newbio245226a0. [DOI] [PubMed] [Google Scholar]
  31. Nicolson G. L., Singer S. J. Ferritin-conjugated plant agglutinins as specific saccharide stains for electron microscopy: application to saccharides bound to cell membranes. Proc Natl Acad Sci U S A. 1971 May;68(5):942–945. doi: 10.1073/pnas.68.5.942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rambourg A., Neutra M., Leblond C. P. Presence of a "cell coat" rich in carbohydrate at the surface of cells in the rat. Anat Rec. 1966 Jan;154(1):41–71. doi: 10.1002/ar.1091540105. [DOI] [PubMed] [Google Scholar]
  33. Ray R. K., Simmons R. L. Differential release of sialic acid from normal and malignant cells by Vibrio cholerae neuraminidase or influenza virus neuraminidase. Cancer Res. 1973 May;33(5):936–939. [PubMed] [Google Scholar]
  34. Salser J. S., Balis M. E. Distribution and regulation of deoxythymidine kinase activity in differentiating cells of mammalian intestines. Cancer Res. 1973 Aug;33(8):1889–1897. [PubMed] [Google Scholar]
  35. Sheahan D. G., Horowitz S. A., Zamcheck N. Deletion of epithelial ABH isoantigens in primary gastric neoplasms and in metastatic cancer. Am J Dig Dis. 1971 Nov;16(11):961–969. doi: 10.1007/BF02235003. [DOI] [PubMed] [Google Scholar]
  36. Stellner K., Hakomori S., Warner G. S. Enzymic conversion of "H1-glycolipid" to A or B-glycolipid and deficiency of these enzyme activities in adenocarcinoma. Biochem Biophys Res Commun. 1973 Nov 16;55(2):439–445. doi: 10.1016/0006-291x(73)91106-6. [DOI] [PubMed] [Google Scholar]
  37. TREVELYAN W. E., PROCTER D. P., HARRISON J. S. Detection of sugars on paper chromatograms. Nature. 1950 Sep 9;166(4219):444–445. doi: 10.1038/166444b0. [DOI] [PubMed] [Google Scholar]
  38. Warren L., Fuhrer J. P., Buck C. A. Surface glycoproteins of cells before and after transformation by oncogenic viruses. Fed Proc. 1973 Jan;32(1):80–85. [PubMed] [Google Scholar]
  39. Whitehead J. S., Bella S., Jr, Kim Y. S. An N-acetylgalactosaminyltransferase from human blood group A plasma. II. Kinetic and physicochemical properties. J Biol Chem. 1974 Jun 10;249(11):3448–3452. [PubMed] [Google Scholar]
  40. Wu H. C., Meezan E., Black P. H., Robbins P. W. Comparative studies on the carbohydrate-containing membrane components of normal and virus-transformed mouse fibroblasts. I. Glucosamine-labeling patterns in 3T3, spontaneously transformed 3T3, and SV-40-transformed 3T3 cells. Biochemistry. 1969 Jun;8(6):2509–2517. doi: 10.1021/bi00834a038. [DOI] [PubMed] [Google Scholar]

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