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Oxygen Consumption and Oxygen Diffusion Properties of Multicellular Spheroids from two Different Cell Lines

  • Wolfgang F. Mueller-Klieser
  • Robert M. Sutherland
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 180)

Abstract

Multicellular spheroids are an in vitro tissue model in which the cells are supplied by diffusion of oxygen and substrates from the environmental growth medium (Sutherland et al., 1971). Since these substances are consumed when diffusing to the spheroid center, their concentration should decrease continuously towards the inner parts of the spheroids. Therefore, the location of the cells within the spheroid is an important determinant of the efficiency of the O2 and nutrient supply. The restriction of the O2 availability in the inner part of the spheroids may influence the metabolic and cell cycle state, and may even cause cell death, indicated by central necrosis in larger spheroids. Also, accumulation of metabolic waste products during spheroid growth may have an impact on cellular metabolism and viability. Multicellular tumor spheroids have been widely used in cancer research to study the interrelationship among metabolism, cell cycle state and response of tumor cells to various treatment modalities. Many of these investigations resulted in the conclusion that the supply of O2 plays a decisive role in controlling the responsiveness to treatment.

Keywords

Oxygen Tension Multicellular Spheroid Multicellular Tumor Spheroid Cell Cycle State Spheroid Growth 
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.

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References

  1. Boag, J. W., 1969, Oxygen diffusion and oxygen depletion problems in radiobiology, Curr. Top. Radiat. Res., 5:141.Google Scholar
  2. Boag, J W., 1977, Oxygen diffusion in tumour capillary networks, Bibl. anat., 15:266.PubMedGoogle Scholar
  3. Burton, A. C., 1966, Rate of growth of solid tumours as a problem of diffusion, Growth, 30:157.PubMedGoogle Scholar
  4. Carlsson, J., Stalnacke, C. G., Acker, H., Haij-Karim, M., Nilsson, S., and Larsson, B., 1979, The influence of oxygen on viability and proliferation in cellular spheroids. Int. J. Radiat. Oncol. Biol. Phys., 5:2011.PubMedCrossRefGoogle Scholar
  5. Deakin, A. S., 1975, Model for the growth of a solid in vitro tumor, Growth, 39:159.PubMedGoogle Scholar
  6. Freyer, J. P., 1981, Heterogeneity in multicell spheroids induced by alterations in the external oxygen and glucose concentration, Thesis, University of Rochester, Rochester, N.Y., USA.Google Scholar
  7. 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
  8. Kasche, V., and Kuhlmann, G., 1980, Direct measurement of the thickness of the unstirred diffusion layer outside immobilized bio-catalysts, Enzyme Microb. Technol., 2:309.CrossRefGoogle Scholar
  9. 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
  10. 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
  11. Mueller-Klieser, W., and Sutherland, R. M., 1982b, Oxygen tensions in multicell spheroids of two cell lines, Brit. J. Cancer, 45:256.PubMedCrossRefGoogle Scholar
  12. 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/Ro multicell tumor spheroids, Adv. Exp. Med. Biol., (in press).Google Scholar
  13. Mueller-Klieser, W., 1983, Theoretical analysis of stationary oxygen tension profiles in multicell spheroids, Naunyn-Schmiedeberg’s Arch. Pharmacol., 322:R50.Google Scholar
  14. Mueller-Klieser, W., submitted, A method for the quantitative evaluation of oxygen tension distributions in multicellular spheroids, Biophys. J., (submitted).Google Scholar
  15. Rashevsky, N., 1960, “Mathematical Biophysics”, Dover Publications, Inc., New York.Google Scholar
  16. Sutherland, R. M., and Durand, Radiation response of multicellular spheroids — an in vitro tumour model, Curr. Top. Radia. Res., 11:87.Google Scholar
  17. Sutherland, R. M., McCredie, J. A., and Inch, W. R., 1971, Growth of multicellular spheroids in tissue culture as a model of nodular carcinomas, J. Natl. Cancer Inst., 46:113.PubMedGoogle Scholar
  18. Thews, G., 1968, The theory of oxygen transport and its application to gaseous exchange in the lung, in: “Oxygen Transport in Blood and Tissue”, D. W. Luebbers, U. C. Luft, G. Thews, and Witzleb, E., eds., Thieme, Stuttgart.Google Scholar
  19. Vaupel, P., 1976, Effect of percentual water content in tissues and liquids on the diffusion coefficients of O2, CO2, N2, and H2. Pfluegers Arch., 361:201.CrossRefGoogle Scholar
  20. Vaupel, P., 1977, Hypoxia in neoplastic tissue, Microvasc. Res., 13:399.PubMedCrossRefGoogle Scholar
  21. Whalen, W. J., Nair, P., and Ganfield, R. R., 1973a, Measurement of oxygen tension in tissues with a micro oxygen electrode, Microvase. Res., 5:254.CrossRefGoogle Scholar
  22. Whalen, W. J., Riley, J., and Nair, P., 1967, A microelectrode for measuring intracellular pO2, J. Appl. Physiol. 23:798.PubMedGoogle Scholar
  23. Whalen, W. J., Savoca, J., and Nair, P., 1973b, Oxygen tension measurement in carotid body of the cat, Amer. J. Physiol., 225:986.PubMedGoogle Scholar
  24. Zander, R., 1976, Cellular oxygen concentration, Adv. Exp. Med. Biol., 75:463.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Wolfgang F. Mueller-Klieser
    • 1
  • Robert M. Sutherland
    • 2
  1. 1.Dept. Applied PhysiologyUniv. of MainzMainzGermany
  2. 2.Dept. Radiation Biology and Biophysics, and Cancer CenterUniv. of RochesterRochesterUSA

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