Determination of Diffusion Constants for Metabolites in Multicell Tumor Spheroids

  • J. P. Freyer
  • R. M. Sutherland
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 159)


Multicell tumor spheroids (MTS) exhibit many of the characteristics of tumors, including central necrosis, heterogeneities in proliferative status and clonogenic capacity, and subpopulations of radiation and chemotherapeutic resistant cells (Freyer and Sutherland, 1980; Sutherland and Durand, 1976). In tumors, control of most of these parameters appears to be due to low molecular eight nutrients such as oxygen and glucose. Tannock (1976) suggested that loss of proliferative activity was correlated with the oxygen diffusion distance. Low values of oxygen partial pressure in tumors are common (Thews and Vaupel, 1974), as are low pH values (Vaupel et al., 1981). Tumor extracellular fluid has been shown to contain low levels of glucose (Guillino, 1975). Most tumors are very heterogeneous with respect to the local microenvironment (Mueller-Klieser et al., 1980) due to the random structure and chaotic functioning of the vascular system. Thus, it has been proven difficult to establish precisely which nutrient(s) are critical for cellular proliferation and viability in vivo.


Extracellular Space Diffusion Constant Uptake Curve Label Medium Clonogenic Capacity 
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  1. 1.
    Freyer, J. P. and Sutherland, R. M. Selective dissociation and characterization of cells from multicell spheroids. Cancer Res. 40: 3956–3965 (1980).PubMedGoogle Scholar
  2. 2.
    Sutherland, R. M. and Durand, R. E. Radiation response of multicell spheroids–an in vitro tumor model. Current Topics Radiat. Res. 11: 87–139 (1976).Google Scholar
  3. 3.
    Tannock, I. F. The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumor. Brit. J. Cancer, 22: 258–273 (1968).PubMedCrossRefGoogle Scholar
  4. 4.
    Thews, G. and Vaupel, P. P02 distribution in tumor tissue of DS-carcinosarcana. Oncology, 30: 475–484 (1974).PubMedCrossRefGoogle Scholar
  5. 5.
    Vaupel, P., Frinak, S. and Bicher, H. I. Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinama. Cancer Res., 41: 2008–2015 (1981).PubMedGoogle Scholar
  6. 6.
    Guillino, P. M. In vivo utilization of oxygen and glucose by neoplastic tissues. Advan. Exp. Med. Biol., 75:521–536 (1975).Google Scholar
  7. 7.
    Muller-Klieser, W., Vaupel, P., Marz, R., and Grunewald, W. A. Intracapillary oxyhemoglobin saturation in malignant tumors with central or peripheral blood supply. Europ. J. Cancer, 16: 195–201 (1980).Google Scholar
  8. 8.
    Carlson, J., Stalnacke, C. G., Acker, H., Haji-Karim, M., Nilsson, S. and Larsson, B. The influence of oxygen on viability and proliferation in cellular spheroids. Int. J. Rad. Oncol. Biol. Phys., 5: 2011–2020 (1979).CrossRefGoogle Scholar
  9. 9.
    Mueller-Klieser, W. and Sutherland, R. M. Influence of convection in the growth medium on oxygen tensions in multicellular tumor spheroids. Cancer Res. 42, 237–242, 1982.PubMedGoogle Scholar
  10. 10.
    Kaufman, N., Bicher, H. A. and Hetzel, F. W. Radiobiolocgical sighificance of microphvsiolocy determinations in spheroids. presented at 29th Annual Meeting of Radiation Research Society, Minneapolis, MN, May 31-June 4, 1981.Google Scholar
  11. 11.
    Franko, H. J. and Sutherland, R. M. Oxygen diffusion distance and development of necrosis in multicell spheroids. Radiat. Res., 79: 439–453 (1979).PubMedCrossRefGoogle Scholar
  12. 12.
    Simon, W. Mathematical Techniques for Biology and Medicine, MIT Press, Inc., Cambridge, MA (1977).Google Scholar
  13. 13.
    Pappius, H. M., Klatzo, I. and Elliott, K. A. C. Further studies on swelling of brain slices. Canad. J. Biochem., 40: 885–898 (1962).Google Scholar
  14. 14.
    Wigle, J. C., Freyer, J. P. and Sutherland, R. M. Use of a sedimentation column to obtain uniformly-sized populations of multicell spheroids, In Vitro, in press, 1983.Google Scholar
  15. 15.
    Addank, I., Cahill, F. D. and Sotos, J. F. A Method for the determination of extracellular space with 3H-inulin. Clin. Chem., 13: 953–957 (1967).Google Scholar
  16. 16.
    Stein, W. D. The Movement of Molecules Across Cell Membranes, Academic Press, Inc., New York, NY (1967).Google Scholar
  17. 17.
    Busmeyer, J., Vaupel, P. and Thews, G. Diffusion constants of glucose in tumor tissue. Pfuegers Arch., 368: 817 (1977).Google Scholar
  18. 18.
    Vaupel, P., Effect of percentual water content in tissues and liquids on diffusion-coefficients of 02, CO2, N2 and H21. Pfulgers Arch., 361, 16 (1976).Google Scholar
  19. 19.
    Kobayashi, T. and Bakay, L. The extracellular space in experimental brain tumors. Acta Neural. Scand., 47: 307–314 (1971).Google Scholar
  20. 20.
    Appelgren, L., Peterson, H. I. and Rosengren, B. Vascular and extravascular spaces in two transplantable tumors of the rat. Bibl. Anat. 12: 504–510 (1973).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • J. P. Freyer
    • 1
  • R. M. Sutherland
    • 1
  1. 1.Department of Radiation Biology and Biophysics and Cancer CenterUniversity of Rochester School of Medicine and DentistryRochesterUSA

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