Advertisement

Changes in O2 Consumption of Multicellular Spheroids During Development of Necrosis

  • W. Mueller-Klieser
  • B. Bourrat
  • H. Gabbert
  • R. M. Sutherland
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 191)

Abstract

Multicellular spheroids are spherical aggregates of cells that are supplied by diffusion of oxygen and substrates from the surrounding growth medium (Sutherland and Durand, 1976). Metabolic waste products are removed from the cells in these aggregates by diffusion into the growth medium. Cells within multicellular spheroids may be exposed to environmental conditions similar to those in tissue located between nutritive microvessels. Thus, tumor spheroids make it possible to study the impact of the tumor-specific micromilieu on cellular metabolism, cell cycle state, cellular viability or response to treatment. Factors in the microenvironment of tumor cells which may be relevant in this regard, are the oxygen tension (PO2), as well as the concentration of hydrogen ions (pH), of glucose and other nutrients, and of metabolic waste products such as lactate. The distribution of PO2-values in spheroids has been assessed by several investigators using O2-sensitive microelec-trodes (Carlsson et al., 1979; Kaufman et al., 1981; Mueller-Klieser and Sutherland, 1982a,b, 1983; Mueller-Klieser et al., 1983;Hetzel and Kaufman, 1983; Mueller-Klieser, 1984a,b).

Keywords

Oxygen Tension Central Necrosis Tumor Spheroid Spinner Flask Multicellular Spheroid 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bush, N.A., Bruley, D.F., and Bicher, H.I., 1983, Identification of viable regions in “in vitro” spheroidal tumors: a mathematical investigation, Adv. Exp. Med. Biol., 157:1.Google Scholar
  2. Carlsson, J., Stalnacke, CG., Acker, H., Haji-Karim, M., Milsson, S., and Larsson, B., 1979, The influence of oxygen on viability and proliferation in cellular spheroids, Int. J. Radiat. Oncol. Biol. Phys., 5:2011.Google Scholar
  3. Franko, A.J., and Sutherland, R.M., 1979, Oxygen diffusion distance and development of necrosis in multicell spheroids, Radiat. Res., 79:439.Google Scholar
  4. Franko, A.J., and Freedman, H.I., 1984, Model of diffusion of oxygen to spheroids grown in stationary medium — I. Complete symmetry, Bull. Math. Biol., 46:205.Google Scholar
  5. Freyer, J.P., 1981, Heterogeneity in multicell spheroids induced by alterations in the external oxygen and glucose concentration, Thesis, University of Rochester, N.Y.Google Scholar
  6. Freyer, J.P., and Sutherland, R.M., 1980, Selective dissociation and characterization of cells from different regions of multicell tumor spheroids, Cancer Res., 40:3956.PubMedGoogle Scholar
  7. Freyer, J.P., Tustanoff, E., Franko, A.J., and Sutherland, R.M., 1984, In situ oxygen consumption rates of cells in V79-multicellular spheroids during growth, J. Cell. Physiol., 118:53.Google Scholar
  8. Grossmann, U., Carlsson, J., and Acker, H., 1983, Oxygen consumption profiles inside cellular spheroids calculated from P -profiles Adv. Exp. Med. Biol., 159:477.Google Scholar
  9. Hetzel, F.W., and Kaufman, N., 1983, Chemotherapeutic drugs as indirect oxygen radiosensitizers, Int. J. Radiat. Oncol. Biol. Phys., 9:751.Google Scholar
  10. Kaufman, N., Bicher, H.I., Hetzel, F.W., and Brown, M., 1981, A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids, Cancer Clin. Trials, 4:199.PubMedGoogle Scholar
  11. Mueller-Klieser, W., 1984a, Microelectrode measurements of oxygen tension distributions in multicellular spheroids cultured in spinner flasks, Rec. Res. Cancer Res., 95:134.Google Scholar
  12. Mueller-Klieser, W., 1984b, A method for the determination of oxygen consumption rates and oxygen diffusion coefficients in multicellular spheroids, Biophys. J., 46:in press.Google Scholar
  13. Mueller-Klieser, W., and Sutherland, R.M., 1982a, Influence of convection in the growth medium on oxygen tensions in multicellular tumor spheroids, Cancer Res., 42:237.PubMedGoogle Scholar
  14. Mueller-Klieser, W., and Sutherland, R.M., 1982b, Oxygen tensions in multicell spheroids of two cell lines, Brit. J. Cancer, 45:256.Google Scholar
  15. Mueller-Klieser, W., and Sutherland, R.M., 1983, Frequency distribution histograms of oxygen tensions in multicell spheroids, Adv. Exp. Med. Biol., 159:497.Google Scholar
  16. Mueller-Klieser, W., and Sutherland, R.M., in press, Oxygen consumption and oxygen diffusion properties of multicellular spheroids from two different cell lines, Adv. Exp. Med. Biol.,Google Scholar
  17. Mueller-Klieser, W., Freyer, J.P., and Sutherland, R.M., 1983, Evidence for a major role of glucose in controlling development of necrosis in EMT6/R0 multicell tumor spheroids, Adv. Exp. Med. Biol., 159:487.PubMedCrossRefGoogle Scholar
  18. Sutherland, R.M., and Durand, R.E., 1976, Radiation response of multicellular spheroids — an in vitro tumour model, Curr. Top. Radiat. Res., 11:87.Google Scholar
  19. Vaupel, P., 1980, Oxygen supply to malignant tumors, in: “Tumor Blood Circulation: Angiogenesis, Morphology and Blood Flow of Experimental and Human Tumors”, H.I. Peterson, ed., CRC Press, Boca Raton.Google Scholar
  20. Whalen, W.J., Riley, J., and Nair, P., 1967, A microelectrode for measuring intracellular PO2, J. Appl. Physiol., 23:798.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • W. Mueller-Klieser
    • 1
  • B. Bourrat
    • 1
  • H. Gabbert
    • 2
  • R. M. Sutherland
    • 1
  1. 1.Dept. of Applied PhysiologyUniversity of MainzMainzGermany
  2. 2.Dept. of PathologyUniversity of MainzMainzGermany

Personalised recommendations