The Altered Metabolism of Sialic-Acid-Containing Compounds in Tumorigenic-Virus-Transformed Cells

  • Peter H. Fishman
  • Roscoe O. Brady


At this point in time, the quest for information regarding phenomena regulating cell growth has focused to a considerable extent on investigations of alterations in the chemical composition of the surfaces of neoplastic cells. Relatively few discoveries have occurred so far in this regard, but the recently observed alteration of ganglioside composition and the underlying metabolic reactions responsible for this change in tumorigenic-virus-transformed cells may prove to be an important contribution in this area. We shall review the nature of these changes in tumorigenic virus transformation in this chapter. We shall also touch upon some differences in glycoprotein metabolism which have recently been observed in these cells, and we shall make some conclusions regarding the significance of the differences between normal and tumorigenic cells.


Sialic Acid Baby Hamster Kidney Rous Sarcoma Virus Altered Metabolism Mouse Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aaronson, S. A., and Weaver, C. A., 1971, Characterization of murine sarcoma virus (Kirsten) transformation of mouse and human cells, J. Gen. Virol. 13: 245.PubMedCrossRefGoogle Scholar
  2. Anderson, W. B., Johnson, G. S., and Pastan, I., 1973a, Transformation of chick-embryo fibroblasts by wild-type and temperature-sensitive Rous sarcoma virus alters adenylate cyclase activity, Proc. Natl. Acad. Sci. U.S. 70: 1055.CrossRefGoogle Scholar
  3. Anderson, W. B., Lovelace, E., and Pastan, I., 1973b, Adenylate cyclase activity is decreased in chick embryo fibroblasts transformed by wild type and temperature sensitive Schmidt-Ruppin Rous sarcoma virus, Biochem. Biophys. Res. Commun. 52: 1293.PubMedCrossRefGoogle Scholar
  4. Babiuk, L. A., and Hudson, J. B., 1973, Integration of polyoma virus DNA into mammalian genomes, Biochem. Biophys. Res. Commun. 47: 111.CrossRefGoogle Scholar
  5. Bader, J. P., and Brown, N. R., 1971, Induction of mutations in an RNA tumor virus by an analogue of a DNA precursor, Nat. New Biol. 234: 11.PubMedGoogle Scholar
  6. Bosmann, H. B., 1972a, Sialyl transferase activity in normal and RNA-and DNA-virus transformed cells utilizing desialyzed, trypsinized cell plasma membrane external surface glycoproteins as exogenous acceptors, Biochem. Biophys. Res. Commun. 49: 1256.PubMedCrossRefGoogle Scholar
  7. Bosmann, H. B., 1972b, Cell surface glycosyltransferases and acceptors in normal and RNA-and DNA-virus transformed fibroblasts, Biochem. Biophys. Res. Commun. 48: 523.PubMedCrossRefGoogle Scholar
  8. Bosmann, H. B., and Eylar, E. H., 1968, Collagen-glucosyl transferase in fibroblasts transformed by oncogenic viruses, Nature 218: 582.PubMedCrossRefGoogle Scholar
  9. Bosmann, H. B., and Winston, R. A., 1970, Synthesis of glycoprotein, glycolipid, protein and lipid in synchronized L5178Y cells, J. Cell. Biol. 45: 23.PubMedCrossRefGoogle Scholar
  10. Brady, R. O., and Mora, P. T., 1970, Alteration in ganglioside pattern and synthesis in SV40 and polyoma virus transformed mouse cell lines, Biochim. Biophys. Acta 218: 308.Google Scholar
  11. Brady, R. O., Kanfer, J. N., and Shapiro, D., 1965, Metabolism of glucocerebrosides II. Evidence of an enzymatic deficiency in Gaucher’s disease, Biochem. Biophys. Res. Commun. 18: 221.PubMedCrossRefGoogle Scholar
  12. Brady, R. O., Borek, C., and Bradley, R. M., 1969, Composition and synthesis of gangliosides in rat hepatocyte and hepatoma cell lines, J. Biol. Chem. 244: 6552.PubMedGoogle Scholar
  13. Brady, R. O., Fishman, P. H., and Mora, P. T., 1973a, Alterations of complex lipid metabolism in tumorigenic virus transformed cell lines, Adv. Enzyme Reg. 11: 231.CrossRefGoogle Scholar
  14. Brady, R. O., Fishman, P. H., and Mora, P. T., 1973b, Membrane components and enzymes in virally transformed cells, Fed. Proc. 32: 102.PubMedGoogle Scholar
  15. Brew, K., Vanaman, T. C., and Hill, R. L., 1968, The role of α-lactalbumin and the A protein in lactose synthetase, a unique mechanism for the control of a biological reaction, Proc. Natl. Acad. Sci. U.S. 59: 491.CrossRefGoogle Scholar
  16. Brown, J. C., 1972, Cell surface glycoprotein I: Accumulation of a glycoprotein on the outer surface of mouse LS cells during mitosis, J. Supermol. Struct. 1: 1.CrossRefGoogle Scholar
  17. Buck, C. A., Glick, M. C., and Warren, L., 1970, A comparative study of glycoproteins from the surface of control and Rous sarcoma virus transformed hamster cells, Biochemistry 9: 4567.PubMedCrossRefGoogle Scholar
  18. Buck, C. A., Glick, M. C., and Warren, L., 1971a, Glycopeptides from the surface of control and virus-transformed cells, Science 172: 169.PubMedCrossRefGoogle Scholar
  19. Buck, C. A., Glick, M. C., and Warren, L., 1971b, Effect of growth on the glycoproteins from the surface of control and Rous sarcoma virus transformed hamster cells, Biochemistry 10: 2176.PubMedCrossRefGoogle Scholar
  20. Critchley, D. R., and Macpherson, I., 1973, Cell density dependent glycolipids in NIL 2 hamster cells, derived malignant and transformed cell lines, Biochem. Biophys. Acta 296: 145.PubMedGoogle Scholar
  21. Cuatrecasas, P., 1973, Interaction of Vibrio cholera enterotoxin with cell membranes, Biochemistry 12: 3547.PubMedCrossRefGoogle Scholar
  22. Culp, L. A., Grimes, W. J., and Black, P. H., 1971, Contact-inhibited revertant cell lines isolated from SV40-transformed cells, J. Cell. Biol. 50: 682.PubMedCrossRefGoogle Scholar
  23. Cumar, F. A., Brady, R. O., Kolodny, E. H., McFarland, V. W., and Mora, P. T., 1970, Enzymatic block in the synthesis of gangliosides in DNA virus-transformed tumorigenic mouse cell lines. Proc. Nat. Acad. Sci. U.S. 67: 757.CrossRefGoogle Scholar
  24. Den, H., Schultz, A. M., Basu, M., and Roseman, S., 1971, Glycosyltransferase activities in normal and polyoma-transformed BHK cells, J. Biol. Chem. 246: 2721.PubMedGoogle Scholar
  25. Dijong, I., Mora, P. T., and Brady, R. O., 1971, Gas chromatographic determination of gangliosides in mouse cell lines and in virally transformed derivative lines, Biochemistry 10: 4039.PubMedCrossRefGoogle Scholar
  26. Diringer, H., Strobel, G., and Koch, M. A., 1972, Glycolipids of mouse fibroblasts and virus transformed mouse cell lines, Hoppe-Seyl. Z. 353: 1759.Google Scholar
  27. Dubbs, D. R., Kitt, S., de Torres, R. A., and Anken, M., 1967, Virogenic properties of bromodeoxyuridine-resistant Simian virus 40-transformed mouse kidney cells, J. Virology 1: 968.PubMedGoogle Scholar
  28. Eckhart, W., 1969, Cell transformation by polyoma virus and SV40, Nature 224: 1069.PubMedCrossRefGoogle Scholar
  29. Epstein, W., and Beckwith, J. R., 1968, Regulation of gene expression, Ann. Rev. Biochem. 37: 411.CrossRefGoogle Scholar
  30. Fishman, P. H., McFarland, V. W., Mora, P. T., and Brady, R. O., 1972, Ganglioside biosynthesis in mouse cells: Glycosyltransferase activities in normal and virally transformed lines, Biochem. Biophys. Res. Commun. 48: 48.PubMedCrossRefGoogle Scholar
  31. Fishman, P. H., Brady, R. O., Bradley, R. M., Aaronson, S. A., and Todero, G. J., 1974, Absence of a specific ganglioside galactosyltransferase in murine sarcoma virustransformed mouse cells, Proc. Natl. Acad. Sci. U.S. 71: 298.CrossRefGoogle Scholar
  32. Fishman, P. H., Brady, R. O., and Mora, P. T., 1973, Altered glycolipid metabolism related to viral transformation of established mouse cell lines, in: Tumor Lipids: Biochemistry and Metabolism (R. Wood, ed.), pp. 251–266, American Oil Chemists Society, Chicago.Google Scholar
  33. Folch, J., Lees, M., and Stanley, G. H. S., 1957, A simple method for the isolation and purification of total lipids from animal tissues, J. Biol. Chem. 226: 497.PubMedGoogle Scholar
  34. Glick, M. C., and Buck, C. A., 1973, Glycoproteins from the surface of metaphase cells, Biochemistry 12: 85.PubMedCrossRefGoogle Scholar
  35. Glick, M. C., Comstock, C. A., Cohen, M. A., and Warren, L., 1971, Membranes of animal cells. VIII. Distribution of sialic acid, hexosamines, and sialidase in the L cell, Biochim. Biophys. Acta 233: 247.PubMedCrossRefGoogle Scholar
  36. Grimes, W. J., 1970, Sialic acid transferases and sialic acid levels in normal and transformed cells, Biochemistry 9: 5083.PubMedCrossRefGoogle Scholar
  37. Grimes, W. J., 1973, Glycosyltransferase and sialic acid levels of normal and transformed cells, Biochemistry 12: 990.PubMedCrossRefGoogle Scholar
  38. Hakomori, S., 1970, Cell density-dependent changes of glycolipid concentrations in fibroblasts and loss of this response in virus-transformed cells, Proc. Natl. Acad. Sci. U.S. 67: 1741.CrossRefGoogle Scholar
  39. Hakomori, S., and Murakami, W. T., 1968, Glycolipids of hamster fibroblasts and derived malignant-transformed cells, Proc. Nat. Acad. Sci. U.S. 59: 254.CrossRefGoogle Scholar
  40. Hakomori, S., Saito, T., and Vogt, P. K., 1971, Transformation by Rous sarcoma virus: Effects on cellular glycolipids, Virology 44: 609.PubMedCrossRefGoogle Scholar
  41. Hakomori, S., Teather, C., and Andrews, H., 1968, Organizational difference of cell surface hematoside in normal and virally transformed cells, Biochem. Biophys. Res. Commun. 33: 563.PubMedCrossRefGoogle Scholar
  42. Hirai, K., and Defendi, V., 1972, Integration of SV40 DNA into the DNA of permissive monkey kidney cells, J. Virol. 9: 705.PubMedGoogle Scholar
  43. Hirano, H., Parkhouse, B., Nicolson, G., Lennox, E. S., and Singer, S. J., 1972, Distribution of saccharide residues on membrane fragments from a myeloma-cell homogenate: its implications for membrane biogenesis, Proc. Natl. Acad. Sci. U.S. 69: 2945.CrossRefGoogle Scholar
  44. Kampine, J. P., Brady, R. O., Kanfer, J. N., Feld, M., and Shapior, D., 1967a, Diagnosis of Gaucher’s disease and Niemann-Pick disease with small samples of venous blood, Science 155: 86.PubMedCrossRefGoogle Scholar
  45. Kampine, J. P., Brady, R. O., Yankee, R. A., Kanfer, J. N., Shapiro, D., and Gal, A. E., 1967b, Sphingolipid metabolism in leukemic leukocytes, Cancer Res. 27: 1312.PubMedGoogle Scholar
  46. Keshgegian, A. A., and Glick, M. C., 1973, Glycoproteins associated with nuclei of cells before and after transformation by a ribonucleic acid virus, Biochemistry 12: 1221.PubMedCrossRefGoogle Scholar
  47. Klenk, H.-D., and Choppin, P. W., 1970, Glycosphingolipids of plasma membranes of cultured cells and an enveloped virus (SV5) found in these cells, Proc. Natl. Acad. Sci. U.S. 66: 57.CrossRefGoogle Scholar
  48. Kolodny, E. H., Brady, R. O., Quirk, J., and Kanfer, J. N., 1970, Preparation of radioactive Tay-Sachs ganglioside labeled in the sialic acid moiety, J. Lipid Res. 11: 144.PubMedGoogle Scholar
  49. Makita, A., and Seyama, Y., 1971, Alterations of Forssman-antigenic reactivity and of monosaccharide composition in plasma membrane from polyoma-transformed hamster cells, Biochim. Biophys. Acta 241: 403.PubMedCrossRefGoogle Scholar
  50. Marin, G., and Littlefield, J. W., 1968, Selection of morphologically normal cell lines from polyoma-transformed BHK 21/13 hamster fibroblasts, J. Virology 2: 69.PubMedGoogle Scholar
  51. Martin, G. S., 1970, Rous sarcoma virus: a function required for the maintenance of the transformed state, Nature 227: 1021.PubMedCrossRefGoogle Scholar
  52. Meezan, E., Wu, H. C., Black, P. H., and Robbins, P. W., 1969, 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 8: 2518.PubMedCrossRefGoogle Scholar
  53. Mora, P. T., 1973, Cell growth regulation, cell selection and the function of the membrane glycolipids, in: Membrane Mediated Information: Function and Biosynthesis of Membrane Lipids and Glycoproteins(P. W. Kent, ed.), pp. 64–84, Oxford University Press, London.Google Scholar
  54. Mora, P. T., Brady, R. O., Bradley, R. M., and McFarland, V. W., 1969, Gangliosides in DNA virus-transformed and spontaneously transformed tumorigenic mouse cell lines. Proc. Nat. Acad. Sci. U.S. 63: 1290.CrossRefGoogle Scholar
  55. Mora, P. T., Cumar, F. A., and Brady, R. O., 1971, A common biochemical change in SV40 and polyoma virus transformed mouse cells coupled to control of cell growth in culture, Virology 46: 60.PubMedCrossRefGoogle Scholar
  56. Mora, P. T., Fishman Bassin, R. H., Brady, R. O., and McFarland, V. W., 1973, Transformation of Swiss 3T3 cells by murine sarcoma virus is followed by decrease in a glycolipid glycosyltransferase, Nature, 2A5: 226.Google Scholar
  57. Ohta, N., Pardee, A. B., McAuslan, B. R., and Burger, M. M., 1968, Sialic acid contents and controls of normal and malignant cells, Biochem. Biophys. Acta 158: 98.PubMedCrossRefGoogle Scholar
  58. Pollack, R. E., Green, H., and Todaro, G. J., 1968, Growth control in cultured cells: Selection of sublines with increased sensitivity to contact inhibition and decreasing tumor-producing ability, Proc. Natl. Acad. Sci. U.S. 60: 126CrossRefGoogle Scholar
  59. Pollack, R. E., Wolman, S., and Vogel, A., 1970, Reversion of virus-transformed cell lines: Hyperploidy accompanies retention of viral genes, Nature 228: 938.PubMedCrossRefGoogle Scholar
  60. Renger, H. C., and Basilico, C., 1972, Mutation causing temperature-sensitive expression of cell transformation by a tumor virus, Proc. Natl. Actid. Sci. U.S. 69: 109.CrossRefGoogle Scholar
  61. Renkonen, O., Gahmberg, C. G., Simons, K., and Kaarianinen, L., 1970, Enrichment of gangliosides in plasma membranes of hamster kidney fibroblasts, Acta Chem. Scand. 24: 733.PubMedCrossRefGoogle Scholar
  62. Robbins, P. W., and MacPherson, I. A., 1971, Control of glycolipid synthesis in cultured hamster cell line, Nature 229: 569.PubMedCrossRefGoogle Scholar
  63. Roseman, S., 1970, The synthesis of complex carbohydrates by multiglycosyltransferase systems and their potential function in intercellular adhesion, Chem. Phys. Lipids 5: 270.PubMedCrossRefGoogle Scholar
  64. Sakiyama, H., and Burge, B. W., 1972, Comparative studies of the carbohydratecontaining components of 3T3 and Simian virus 40 transformed 3T3 Mouse fibroblasts, Biochemistry 11: 1366.PubMedCrossRefGoogle Scholar
  65. Sakiyama, H., Gross, S. K., and Robbins, P. W., 1972, Glycolipid synthesis in normal and virus-transformed hamster cell lines, Proc. Natl. Acad. Sci. U. S. 69: 872.CrossRefGoogle Scholar
  66. Sakiyama, H., and Robbins, P. W., 1973, Glycolipid synthesis and tumorigenicity of clones isolated from the Nil-2 line of hamster embryo fibroblasts, Red. Proc. 32: 86.Google Scholar
  67. Sambrook, J., Westphal, H., Srinivassan, P. R., and Dulbecco, R., 1968, the integrated state of viral DNA in SV40-transformed cells, Proc. Natl. Acad. Sci. U.S. 60: 1288.CrossRefGoogle Scholar
  68. Sheinin, R., and Onodera, K., 1972, Studies of the plasma membrane of normal and virustransformed 3T3 mouse cells, Biochim. Biophys. Acta 274: 49.PubMedCrossRefGoogle Scholar
  69. Sheinin, R., Onodera, K., Yogeeswaran, G., and Murray, R. K., 1971, Studies of components of the surface of normal and virus-transformed mouse cells, in: The Biology of Oncogenic Viruses 2nd LePetit Symposium (L. G. Silvestri, ed.), pp. 274–285.Google Scholar
  70. Singer, S. J., and Nicolson, G. L., 1972, The fluid mosaic model of the structure of cell membranes, Science 175: 720.PubMedCrossRefGoogle Scholar
  71. Smith, H. S., Sher, C. D., and Todaro, G. J., 1971, Induction of cell division in medium lacking serum growth factor by SV40, Virology 44: 359.PubMedCrossRefGoogle Scholar
  72. Takemoto, K. K., Ting, R. C. Y., Ozer, H. L., and Fabish, P., 1968, Establishment of a cell line from an inbred mouse strain for viral transformation studies: Simian virus 40 transformation and tumor production, J. Natl. Cancer Inst. 41: 1401.PubMedGoogle Scholar
  73. Tomkins, G. M., and Martin, D. W., Jr., 1970, Hormones and gene expression, Ann. Rev. Genet. 4: 91.PubMedCrossRefGoogle Scholar
  74. Warren, L., Critchley, D., and MacPherson, I., 1972a, Surface glycoproteins and glycolipids of chicken embryo cells transformed by a temperature-sensitive mutant of Rous sarcoma virus, Nature 235: 275.PubMedCrossRefGoogle Scholar
  75. Warren, L., Fuhrer, J. P., and Buck, C. A., 1972b, Surface glycoproteins of normal and transformed cells: A difference determined by sialic acid and growth-dependent sialyl transferase, Proc. Natl. Acad. Sci. U.S. 69: 1838.CrossRefGoogle Scholar
  76. Warren, L., Fuhrer, J. P., and Buck, C. A., 1973, Surface glycoproteins of cells before and after transformation by oncogenic viruses, Fed. Proc. 32: 80.PubMedGoogle Scholar
  77. Weil, R., and Kara, J., 1970, Polyoma “tumor antigen”: An activator of chromosome replication?, Proc. Natl. Acad. Sci. U.S. 67: 1011.CrossRefGoogle Scholar
  78. Weinstein, D. B., Marsh, J. B., Glick, M. C., and Warren, L., 1970, Membranes of animal cells. VI. The glycolipids of the L cell and its surface membrane, J. Biol. Chem. 245: 328.Google Scholar
  79. Weiss, M., Ephrussi, B., and Scaletta, L., 1968, Loss of T-antigen from somatic hybrids between mouse cells and SV-40 transformed human cells, Proc. Natl. Acad. Sci. U.S. 59: 1132.CrossRefGoogle Scholar
  80. Wu, H. C., Meezan, E., Black, P. H., and Robbins, P. W., 1969, 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 SV40-transformed 3T3 cells, Biochemistry 8: 2509.PubMedCrossRefGoogle Scholar
  81. Yogeeswaran, G., Sheinin, R., Wherett, J. R., and Murray, R. K., 1972, Studies on the glycosphingolipids of normal and virally transformed 3T3 mouse fibroblasts, J. Biol. Chem. 247: 5146.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Peter H. Fishman
    • 1
  • Roscoe O. Brady
    • 1
  1. 1.Developmental and Metabolic Neurology Branch, National Institute of Neurological Diseases and StrokeNational Institutes of HealthBethesdaUSA

Personalised recommendations