Abstract
The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by ftuorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I–III gliomas had a glucose consumption rate of 2–3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measuredin situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the gliomaderived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomasin situ and (2) are significantly altered in several aspects of their glycolytic metabolism.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allen, N. (1957). Cytochrome oxidase in human brain tumors.J. Neurochem. 2: 37–44.
Allen, N. (1982). Oxidative metabolism of brain tumors.Prog. Exp Tumor Res. 17: 192–209.
Bennett, M. J., Ogilvy, K. M., Blake, G. M., Lewtas, N., and Timperley, W. R. (1976). A study of the glycolytic and pentose phosphate shunt enzymes in relationship to the altered permeability of the blood-brain barrier.J. Neurochem. 26: 1139–1143.
Bigner, D. D., Bigner, S. H., Ponten, J., Westermark, B., Mahaley, M. S., Ruoslahti, E., Herschman, H., Eng, L. F., and Wikstrand, C. J. C. (1981). Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas.J. Neuropathol. Exp. Neurol. 40: 201–229.
Black, P. McL., Kornblith, P. L., Davison, P. F., Liszczak, T. M., Merk, L. P., Smith, B. H., McKeever, P. E., and Quindlen, E. A. (1982). Immunological, biochemical, ultrastructural and electrophysiological characteristics of a human glioblastoma-derived cell culture line.J. Neurosurg. 56: 62–72.
Brierley, J. B., and McIlwain, H. (1956). Metabolic properties of cerebral tissues modified by neoplasia and by freezing.J. Neurochem. 1: 109–118.
Coleman, M. T., and Allen, N. (1978). The hexose monophosphate pathway in ethylnitrosourea induced tumors of the nervous system.J. Neurochem. 30: 83–89.
Cummins, C. J., Lust, W. D., and Passonneau, J. V. (1983a). Regulation of glycogen metabolism in primary and transformed astrocytes in vitro.J. Neurochem. 40: 128–136.
Cummins, C. J., Lust, W. D., and Passonneau, J. V. (1983b). Regulation of glycogenolysis in transformed astrocytesin vitro. J. Neurochem.40: 137–144.
Cummins, C. J., Smith, B. H., and Kornblith, P. L. (1984). Biochemistry of brain tumors. In Wilkins, R. H., and Rengachery, S. S. (eds.),Neurosurgery, Chap. 56, McGraw-Hill, New York, pp. 472–494.
DeLaPaz, R., Di Chiro, G., Smith, B. H., Kornblith, P. L., Quindlen, E. A., Sokoloff, L., Brooks, R. A., Kessler, R. M., Johnston, G. S., Manning, R. G., Flynn, R. M., Wolf, A. P., Fowler, J. S., Brill, B., Blasberg, R. G., London, W. T., Sever, J. L., Kufta, C. V., Reith, K. G., Goble, J. C., and Cummins, C. J. (1981). [18F]-2-fluoro-2-deoxyglucose positron emission tomography of human cerebral gliomas.Abstr. Am. Assoc. Neurol. Surg. 29: 30.
Di Chiro, G., DeLaPaz, R. L., Brooks, R., Sokoloff, L., Kornblith, P. L., Smith, B. H., Patronas, N. J., Kufta, C. V., Kessler, R. M., Johnston, G. S., Manning, R. G., and Wolf, A. P. (1982). Glucose utilization of cerebral gliomas measured by [18F]fluorodeoxyglucose and positron emission tomography.Neurology 32: 1323–1329.
Dominguez, J. E., Graham, J. F., Cummins, C. J., Loreck, D. J., Van der Feen, J., Galarraga, J., DeLaPaz, R., and Smith, B. H. (1987). Enzymes of glucose metabolism in cultured human gliomas: Neoplasia is accompanied by altered hexokinase, phosphofructokinase, and glucose-6-phosphate dehydrogenase levels.Metab. Brain Dis. (in press).
Ereci, N. M., and Silver, I. A. (1986). The role of glial cells in regulation of neorotransmitter amino acids in the external environment. I. Transmembrane electrical and ion gradients and energy parameters in cultured glial-derived cell lines.Brain Res. 26: 193–202.
Grumberger, G., Lowe, W. L., Jr., McElduff, A., and Glick, R. P. (1986). Insulin receptor of human cerebral gliomas: Structure and function.J. Clin. Invest. 77(3): 997–1005.
Heller, I. H., and Elliot, K. A. C. (1955). The metabolism of normal brain and human gliomas in relationship to cell type and density.Can. J. Biochem. Physiol. 33: 395–403.
Kennedy, P. G. E., Lisak, R. P., and Raff, M. C. (1980). Cell type specific markers for human glial and neuroglial cells in culture.Lab. Invest. 43: 342–351.
Kirsch, W. M. (1965). Substrates of glycolysis in intracranial tumors during complete ischemia.Cancer Res. 25: 432–439.
Kirsch, W. M., and Leitner, J. W. (1967). A comparison of the anaerobic glycolysis of human brain and glioblastoma.J. Neurosurg. 27: 45–51.
Kornblith, P. L. (1978). Role of tissue culture in prediction of malignancy.Clin. Neurosurg. 25: 346–376.
Kornblith, P. L. (1980). Role of tissue culture in prediction of malignancy.Clin. Neurosurg. 23: 346–376.
Kornblith, P. L., and Szypko, P. (1978). Variations in response to human brain tumors to BCNUin vitro. J. Neurosurg.48: 580–586.
Levin, V. A., Freeman-Dove, M., and Landahl, H. D. (1975). Permeability characteristics of brain adjacent to tumors in rats.Arch. Neurol. 32: 785–791.
Loreck, D. J., Cummins, C. J., Van de Feen, J., Galarraga, nJ., Phang, J. M., and Smith, B. H. (1987). Regulation of the pentose phosphate pathway in human astrocytes and gliomas.Metab. Brain Dis. (in press).
Lowry, O. H., and Passonneau, J. V. (1972).A Flexible System of Enzymatic Analysis, Academic Press, New York.
Lowry, O. H., Rosebrough, N., Farr, A. L., and Randall, R. (1951). Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193: 265–275.
Lowry, O. H., Passonneau, J. V., Hasselberger, F. X., and Schulz, D. W. (1964). Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain.J. Biol. Chem. 239: 18–30.
Lowry, O. H., Berger, S. J., Chi, M. M.-Y., Carter, J. G., Blackshaw, A., and Outlaw, W. (1977). Diversity of metabolic patterns in human brain tumors. I. High energy phosphate compounds and basic composition.J. Neurochem. 29: 959–977.
Lowry, O. H., Berger, S. J., Carter, J. G., Chi, M. M.-Y., Manchester, J. K., Knor, J., and Pusateri, M. E. (1983). Diversity of metabolic patterns in human brain tumors: Enzymes of energy cofactors.J. Neurochem. 41: 994–1010.
Lund-Andersen, H. (1979). Transport of glucose from blood to brain.Physiol. Rev. 59: 305–352.
Lust, W. D., Schwartz, J. P., and Passonneau, J. V. (1975a). Glycolytic metabolism in cultured cells of the nervous system. I. Glucose transport and metabolism in the C-6 glioma cell line.Mol. Cell. Biochem. 8: 169–176.
Lust, W. D., Passonneau, J. V., and Crites, S. (1975b). The measurement of glycogen in tissue by amyloalpha-1,4-alpha-1,6 glucosidase after destruction of preexisting glucose.Anal. Biochem. 68: 328–331.
Mahaley, M. S. (1966). Thein vitro respiration of normal brain and brain tumors.Cancer Res. 26: 195–197.
Naruse, S., Horikawa, Y., Tanaka, C., Higuchi, T., Ueda, S., Hirakawa, K., Nishikawa, H., and Watari, H. (1985). Observations of energy metabolism in neuroectodermal tumors usingin vivo 31P-NMR.Magnet. Reson. Imag. 3(2): 117–123.
Passonneau, J. V., Schwartz, J. P., and Lust, W. D. (1978). Some aspects of the intermediary metabolism of glioma cells in culture. In Schoffeniels, E.,et. al. (eds.),Dynamic Properties ofGlia Cells in Culture, Pergamon Press, Oxford, pp. 133–142.
Perria, L., Viale, G., Ibba, F., Andreussi, L., and Viale, E. (1964). Istocitochimica dei tumori endocranici.Neuropsichiatria 20: 419–523.
Ponten, J. (1975). Neoplastic human glia cells in culture. In Fogh, J. (ed.),Human Tumor Cells in Vitro, Plenum Press, New York, pp. 175–204.
Ponten, J., and Westermark, B. (1978). Properties of human malignant glioma cellsin vitro. Med. Biol.56: 184–193.
Schwartz, J. P., and McCandless, D. W. (1976). Glycolytic metabolism in cultured cells of the nervous system. IV. The effects of thiamine deficiency on thiamine levels, metabolites and thiamine-dependent enzymes of the C-6 glioma and C-1300 neuroblastoma cell lines.Mol. Cell. Biochem.13: 49–52.
Schwartz, J. P., Lust, W. D., Lauderdale, V. R., and Passonneau, J. V. (1975). Glycolytic metabolism in cultured cells of the nervous system. II. Regulation of pyruvate and lactate metabolism in the C-6 glioma cell line.Mol. Cell. Biochem. 9: 67–72.
Steel, G. G. (1980). Growth kinetics of brain tumors. In Thomas, D. G. T., and Graham, D. I. (eds.),Brain Tumors. Scientific Basis, Clinical Investigation and Current Therapy, Butterworth, Boston, pp. 10–20.
van Veelen, C. W. M., Verbiest, H., Zulch, K. J., van Ketel, B., van der Vlist, M. J. M., Vlug, A. M. C., Rijksen, G., and Staal, G. E. (1979). L-Alpha-alanine inhibition of pyruvate kinase from tumors of the human central nervous system.Cancer Res. 39: 4263–4269.
van Veelen, C. W. M., Verbiest, H., Zulch, K. J., van Ketel, B., van der Vlist, M. J. M., and Vlug, A. M. C. (1982). Pyruvate kinase in human brain tumors. Significance in the treatment of gliomas.Acta Neurochirug. 61: 145–159.
Viale, F. L. (1980). Biochemical patterns in brain tumors. II. Enzymes of the tricarboxylic cycle.Acta Neurochir.20: 273–279.
Victor, J. V., and Wolf, A. (1937). Metabolism of brain tumors.Proc. Assoc. Res. Nerv. Ment. Dis. 16: 44–58.
Warburg, O. (1956). On the origin of cancer cells.Science 123: 309–315.
Weber, G. (1977). Enzymology of cancer cells.N. Engl. J. Med. 296: 486–493.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galarraga, J., Loreck, D.J., Graham, J.F. et al. Glucose metabolism in human gliomas: Correspondence ofin situ andin vitro metabolic rates and altered energy metabolism. Metabolic Brain Disease 1, 279–291 (1986). https://doi.org/10.1007/BF00999357
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00999357