Journal of Neuro-Oncology

, Volume 16, Issue 2, pp 109–115 | Cite as

Quantitative analysis of copper, zinc and copper/zinc ratio in selected human brain tumors

  • Daizo Yoshida
  • Yukio Ikeda
  • Shozo Nakazawa
Laboratory Investigation

Summary

Serum copper and zinc concentrations and copper/zinc ratios have been shown to be increased in several types of human malignancies, including human brain tumors. In this study, copper and zinc levels and copper/zinc ratios were determined by atomic absorption analysis in tissue and serum from 29 primary and metastatic brain tumor patients. Metastatic carcinomas and malignant gliomas revealed significantly higher tissue copper concentrations than control tissues and meningiomas. Malignant gliomas demonstrated significantly higher tissue copper/zinc ratios. Both serum copper and copper/zinc ratio were significantly higher in the metastatic carcinoma group than control; however, serum copper levels in malignant glioma patients were not significantly different from control tissues. There were no differences both in the serum and the tissue concentrations of these trace elements in meningiomas and controls. These data suggested that copper, an important angiogenic factors, is accumulated within the malignant tissues of metastatic carcinoma and malignant glioma, but not meningiomas. These findings may have implications regarding angiogenesis in these tumors.

Key words

angiogenesis brain tumor copper zinc 

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References

  1. 1.
    Weinstein I: Current concepts in mechanism of clinical carcinogenesis. Bull NY Acad Med 54: 366–383, 1978Google Scholar
  2. 2.
    Springatte C, Mildvan A, Abramson R, Engle J, Loeb L: Eischerichia coli deoxyribonucleic acid polymerase 1, a zinc metalloenzyme. J Biol Chem 248: 5987–5993, 1973Google Scholar
  3. 3.
    Hisaki T, Furumoto T, Nozaka K, Kono K, Odachi T, Mizumoto K, Nishimura O, Koga S: Serum zinc and copper changes after gastrectomy in aged patients with gastric cancer. Jpn J Surg 18: 158–163, 1988Google Scholar
  4. 4.
    Danks D: Copper deficiency in humans. Annu Rev Nutr 8: 235–257, 1988Google Scholar
  5. 5.
    Brem S, Tsanaclis A, Zagzag D: Anticopper treatment inhibits pseudopodial protrusion and the invasive spread of 9L gliosarcoma cells in the rat brain. Neurosurgery 26: 391–396, 1990Google Scholar
  6. 6.
    Brem S, Zagzag D, Tsanaclis A, Brien S: Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by Penicillamine and depletion of copper, an angiogenic cofactor. AJP137: 1121–1142, 1990Google Scholar
  7. 7.
    Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442–447, 1987Google Scholar
  8. 8.
    Zagzag D, Goldenberg M, Brem S: Angiogenesis and bloodbrain barrier breakdown modulate CT contrast enhancement: An experimental study in a rabbit brain tumor model. AJNR10:1989Google Scholar
  9. 9.
    Gray B, Walker CRB: Use of serum copper/zinc ratio in patients with large bowel cancer. J Surg Onco 21: 230–232, 1982Google Scholar
  10. 10.
    Poukkula A, Hakala M, Huhti E: Serum copper, zinc and ceruloplasmin concentrations in patients with lung cancer. Respiration 51: 272–276, 1987Google Scholar
  11. 11.
    Rizk S, Sky-Peck H: Comparison between concentrations of trace elements in normal and neoplastic human breast cancer. Cancer Res 44: 5390–5394, 1984Google Scholar
  12. 12.
    Canelas H, DeJorge F, Pereira W, Sallum J: Biochemistry of cerebral tumors: sodium, potassium, calcium, phosphorus, magnesium, copper and sulphur contents of astrocytomata, medulloblastoma and glioblastomata multiforme. J Neurochem 15: 1455–1461, 1968Google Scholar
  13. 13.
    Kaiser J, Gullotta F: Estimation of copper content of astrocytoma and glioblastoma by cupran method. Neurochirurgia (Stuttgart) 23: 20–23, 1980Google Scholar
  14. 14.
    Lightman A, Brandes J, Binur N, Dugan A, Zinder O: Use of serum copper/zinc ratio in the differential diagnosis of ovarian malignancy. Clin Chem 32: 101–103, 1986Google Scholar
  15. 15.
    Cavallo F, Gerber M, Marubini E, Richardoson S, Barbieri A, Costa A, Pecarli A, Pujol H: Zinc and copper in breast cancer, a joint study in nothern Italy and southern France. Cancer 67: 738–745, 1991Google Scholar
  16. 16.
    Dewis W, Pories W: Inhibition of spectrum of animal tumors by dietary zinc deficiency. J Natl Cancer Inst 48: 375–381, 1972Google Scholar
  17. 17.
    Fenton M, Burke J: Subcellular zinc distribution in livers and tumors of plasmocytoma-bearing mice. Nutrition Research 5: 1383–1391, 1985Google Scholar
  18. 18.
    Fisher G: Function and homeostasis of copper and zinc in mammals. Sci Total Environ 4: 373–412, 1975Google Scholar
  19. 19.
    Gubler C, Lahey M, Cartwright C, Wintrobe M: The transportation of copper in blood. J Clin Invest 32: 405–413, 1953Google Scholar
  20. 20.
    Frieden E: The ferrous to ferric cycles in ion metabolism. Nutr Rev 31: 41–44, 1973Google Scholar
  21. 21.
    McCarthy J, Basara M, Palm S, Sas D, Furcht L: The role of cell adhesion proteins — laminin and fibronectin — In the movement of malignant and metastatic cells. Cancer Metastat Rev 4: 125–152, 1985Google Scholar
  22. 22.
    Rutka J, Myatt C, Giblin J, Davis R, Rosenblum M: Distribution of extracellular matrix proteins in primary human brain tumors: an immunohistochemical analysis.Google Scholar
  23. 23.
    Gullino P: Considerations on the mechanisms of the angiogenic response. Anticancer Res 6: 153–158, 1986Google Scholar
  24. 24.
    Diez M, Cerdrân F, Arroroyo M, Baibrea J: Use of copper/zinc ratio in the diagnosis of lung cancer. Cancer 63: 726–730, 1989Google Scholar
  25. 25.
    Hrgovcic M, Tessmer C, Thomas F, Fuller M, Gamble G, Shullenberger C: Significance of serum copper level in adult patients with Hodgkin's disease. Cancer 37: 1337–1345, 1973Google Scholar
  26. 26.
    Fisher G, Byers V, Shifrine M, Levine A: Copper and zinc levels in serum from human patients with sarcomas. Cancer 37: 356–363, 1976Google Scholar
  27. 27.
    Tureky L, Kalina P, Uhliková E, Nàmerovà S, Krizùko J: Serum ceruloplasmin and copper levels in patients with primary brain tumors. Klin Wochenschr 62: 187–189, 1984Google Scholar
  28. 28.
    Challa V, Moody D, Marshall R, Kelly D: The vascular component in meningiomas associated with severe edema. Neurosurgery 7: 363–368, 1980Google Scholar

Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • Daizo Yoshida
    • 1
  • Yukio Ikeda
    • 1
  • Shozo Nakazawa
    • 1
  1. 1.Department of NeurosurgeryNippon Medical SchoolTokyoJapan
  2. 2.Section of Neurological Surgery, TMP # 416BYale University School of MedicineNew HavenUSA

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