Journal of Neuro-Oncology

, Volume 24, Issue 2, pp 153–161 | Cite as

Metabolic patterns in malignant gliomas

  • Jürgen Meixensberger
  • Birgit Herting
  • Wolfgang Roggendorf
  • Heinz Reichmann
Laboratory Investigation

Summary

Changes of mitochondrial and cytoplasm tumor metabolism were studied in malignant gliomas and normal cortex probesin vitro. By spectrophotometric methods marker enzymes of different mitochondrial (whole respiratory chain, citrate acid cycle, fatty oxidation) and cytoplasm (glycolysis, pentose phosphate shunt) metabolic energy pathways were analysed. Generally, the activities of intramitochondrial key enzymes were significantly decreased in gliomas when compared with enzyme activities of normal cortex tissue (p < 0.01). Glycolytic enzymes and a representative of the pentose phosphate shunt were unchanged or increased. Ratios of marker enzymes of the glycolytic pathway (lactate dehydrogenase) and glycose-6-P dehydrogenase revealed a significant difference between glioblastomas (p < 0.05) and grade III (p < 0.05) tumors in comparison to normal astrocytic tissue and astrocytomas WHO grade II. Thus, biochemical analyses allow metabolic grading of gliomasin vitro and may be a useful tool for understanding tumor biology.

Key words

metabolism glycolysis mitochondrial function brain tumors gliomas 

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References

  1. 1.
    Allen IV, McClure J, McCormick D, Gleadhill CA: LDH isoenzyme pattern in a meningioma with pulmonary metastases. J Pathol 123: 187–191, 1977Google Scholar
  2. 2.
    Allen N: Oxidative metabolism of brain tumors. Prog Exp Tumor Res 17: 192–209, 1972Google Scholar
  3. 3.
    Bustamante E, Morris HP, Pedersen PL: Hexokinase: the direct link between mitochondrial and glycolytic reactions in rapidly growing cancer cells. Adv Exp Med Biol 92: 363–380, 1978Google Scholar
  4. 4.
    Bücher TH, Luh W, Pette D: Einfache und zusammengesetzte optische Tests mit Pyridinnucleotiden. In: Handbuch der physiologisch-chemischen Analyse, 10. Aufl., Bd VI/A, Hoppe-Seyler, Thierfelder 292–339, 1964Google Scholar
  5. 5.
    Di Chiro G: Positron emission tomography using (18F) fluorodeoxyglucose in brain tumors: a powerful diagnostic and prognostic tool. Invest Radiol 22: 360–371, 1987Google Scholar
  6. 6.
    Di Chiro G, Brooks RA, Patronas NJ, Bairamian D, Kornblith PL, Smith BH, Mansi L, Barker J: Issues of thein vivo measurement of glucose metabolism of human central nervous system tumors. Ann Neurol (Suppl) 15: 138–146, 1984Google Scholar
  7. 7.
    Di Chiro G, Brooks RA, Sokoloff L: Glycolytic rate and histologie grade of human cerebral gliomas: a study with 18F-fluorodeoxyglucose and positron emission tomography. In: Heiss WD, Phelps ME (eds) Positron emission tomography of the brain, Springer-Verlag, Berlin-Heidelberg-New York 181–191, 1983Google Scholar
  8. 8.
    Di Chiro G, De La Paz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP: Glucose utilization of cerebral gliomas measured by (18F)-fluorodeoxyglucose and positron emission tomography. Neurology 32: 1323–1329, 1982Google Scholar
  9. 9.
    Di Chiro G, Hatazawa J, Katz DA: Glucose utilization by intracranial meningiomas as an index of tumor aggressivity and probability of recurrence: a PET study. Radiology 164: 521–526, 1987Google Scholar
  10. 10.
    Gerhardt W, Clausen J, Christensen E, Riishede J: Changes of LDH-isoenzymes, esterases, acid phosphatases and proteins in malignant and benign human brain tumors. Acta Neurol Scand 39: 85–111, 1963Google Scholar
  11. 11.
    Heller I, Elliott KAC: The metabolism of normal brain and human gliomas in relation to cell type and density. Can J Biochem Physiol 33: 395–403, 1955Google Scholar
  12. 12.
    Herholz K, Ziffing P, Staffen W: Uncoupling of hexose transport and phosphorylation in human gliomas demonstrated by PET. Eur J Cancer Clin Oncol 24: 1139–1150, 1988Google Scholar
  13. 13.
    Ikezaki K, Black KL, Conklin SG, Becker DP: Glucose in glioma utilized via pentose-phosphate shunt for DNA synthesis. Annual Meeting American Association of Neurological Surgeons 20–25 May 1991 Poster 1354,1991Google Scholar
  14. 14.
    Kameyama M, Tsurumi Y, Shirane R: 18F-Fluoro-2′-deoxyridine and brain tumors: a new approach to nucleic acid metabolism by ARG and PET. J Cereb Blood Flow Metab 7 (Suppl 1): 459, 1987Google Scholar
  15. 15.
    Kameyama M, Tsurumi Y, Shirane R: Multi-parametric analysis of brain tumor with PET. J Cereb Blood Flow Metab 7 (Suppl 1): 466, 1987Google Scholar
  16. 16.
    Kornblith PL: Metabolic studies of brain tumorsin vivo. In: Salcman M (ed) Neurobiology of brain tumors. Williams & Wilkins 4: 251–258,1991Google Scholar
  17. 17.
    Kornblith PL, Cummins CJ, Smith BH, Brooks RA, Patronas NJ, Di Chiro G: Correlation of experimental and clinical studies of metabolism by PET scanning. Prog Exp Tumor Res 27: 170–178, 1984Google Scholar
  18. 18.
    Lichtor T, Dohrmann GJ, Getz GS: Respiratory deficiency and increase glycolysis of benign human brain tumors. Surg Forum 35: 486–488, 1984Google Scholar
  19. 19.
    Lichtor T, Dohrmann GJ: Respiratory patterns in human brain tumors. Neurosurgery 19: 896–899, 1986Google Scholar
  20. 20.
    Lichtor T, Dohrmann GJ: Oxidative metabolism and glycolysis in benign brain tumors. J Neurosurg 67: 336–340, 1987Google Scholar
  21. 21.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 199: 265–275, 1951Google Scholar
  22. 22.
    Lowry OH, Berger SJ, Chi MM-Y, Carter JG, Blackshaw A, Outlaw W: Diversity of metabolic patterns in human brain tumors. I. High energy phosphate compounds and basic composition. J Neurochem 29: 959–977, 1977Google Scholar
  23. 23.
    Lowry OH, Berger SJ, Carter JG, Chi MM-Y, Manchester JK, Knor J, Pusateri ME: Diversity of metabolic patterns in human brain tumors: Enzymes of energy metabolism and related metabolites and cofactors. J Neurochem 41: 994–1010, 1983Google Scholar
  24. 24.
    MacCormick K, Allen IV: Value of LDH isoenzymes in the rapid diagnosis of brain tumors. Neuropathol Appl Neurobiol 2: 269–278, 1976Google Scholar
  25. 25.
    Mahaley MS Jr: Thein vitro respiration of normal brain and brain tumors. Cancer Res 26: 195–197, 1966Google Scholar
  26. 26.
    Marzatico F, Curti D, Dagani F, Silvanvi V, Gaetani P, Butti G, Knerich R: Enzymes related to energy metabolism in human gliomas. J Neurosurg Sci 30: 129–132, 1986Google Scholar
  27. 27.
    Meixensberger J, Herting B, Reichmann H, Roggendorf W: Mitochondrial and cytoplasmatic metabolism in malignant gliomas. J Cancer Res Clin Oncol (Suppl) 188: 120, 1992Google Scholar
  28. 28.
    Minn H, Joensur H, Ahonen A, Klemi P: Fluorodeoxyglucose imaging —a method to assess the proliferative activity of human cancerin vivo — comparison with DNA-flowcy-tometry in head and neck tumors. Cancer 61: 1776–1781, 1988Google Scholar
  29. 29.
    Patronas NJ, Di Chiro G, Kafta C: Prediction of survival in glioma patients by means of positron emission tomography. J Neurosurg 62: 816–822, 1985Google Scholar
  30. 30.
    Pedersen PL: Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res 22: 190–274, 1978Google Scholar
  31. 31.
    Pette D, Reichmann H: A method for quantitative extraction of enzymes and metabolites from tissue samples in the milligram range. J Histochem Cytochem 30: 401–402, 1982Google Scholar
  32. 32.
    Reichmann H, Srihari TH, Pette D: Ipsiand contralateral fibre transformations by cross-reinnervation. A principle of symmetry. Pflügers Arch 397: 202–208, 1983Google Scholar
  33. 33.
    Reichmann H, Hoppeier H, Mathieu-Costello O, von Bergen F, Pette D: Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflügers Arch 404: 1–9, 1985Google Scholar
  34. 34.
    Reichmann H, Maltese WA, De Vivo DC: Enzymes of fatty acid β-oxidation in developing brain. J Neurochem 51: 339–344, 1988Google Scholar
  35. 35.
    Sottocasa GL, Kuylenotiema B: An electron transport system associated with the outer membrane of the mitochondria. J Cell Biol 32: 415–438, 1967Google Scholar
  36. 36.
    Stavrou D, Knedel M, Weidenbach W: Vergleichende Aspekte bezüglich Aktivität und Isoenzymmuster der Lactatdehydrogenase bei spontanen und experimentellen Hirngliomen. Neuropat Pol X 2: 181–188, 1972Google Scholar
  37. 37.
    Viale GL. Andreossi L: Histochemical study of the oxidative activity on tumors of the nervous system. Acta Neuropathol 4: 538–558, 1965Google Scholar
  38. 38.
    Viale GL: Biochemical patterns in brain tumors. I. Enzymes of glycolysis. Acta Neurochir 20: 263–272, 1969Google Scholar
  39. 39.
    Victor JV, Wolf A: Metabolism of brain tumors. Res Publ Assoc Res Nerv Ment Dis 16: 44–58, 1937Google Scholar
  40. 40.
    Warburg O: The metabolism of tumors. Arnold Constable, London: 75–327, 1930Google Scholar
  41. 41.
    Warburg O: On the origin of cancer cells. Science 123: 309–314, 1956Google Scholar
  42. 42.
    Watanabe A, Tanaka R, Takeda N, Washiyama K: DNAsynthesis, blood-flow, and glucose-utilization in experimental rat brain tumors. J Neurosurg 70: 86–91, 1989Google Scholar
  43. 43.
    Weber G: Enzymology of cancer cells. I. N Engl J Med 296: 486–493, 1977Google Scholar
  44. 44.
    Weinhouse S: Oxidative metabolism of neoplastic tissue. Advances Cancer Res 3: 269–325, 1955Google Scholar
  45. 45.
    Wharton DC, Tzagoloff A: Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10: 245–250, 1967Google Scholar
  46. 46.
    Zülch KJ: Histological typing of tumors of the central nervous system, World Health Organization, Geneva. International histological classification of tumors, no. 21, 1979Google Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Jürgen Meixensberger
    • 3
  • Birgit Herting
    • 1
  • Wolfgang Roggendorf
    • 2
  • Heinz Reichmann
    • 1
  1. 1.Department of NeurologyUniversity WürzburgGermany
  2. 2.Department of NeuropathologyUniversity WürzburgGermany
  3. 3.Department of NeurosurgeryUniversity WürzburgGermany

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