Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 1984 Sep;46(3):343–348. doi: 10.1016/S0006-3495(84)84030-8

Method for the determination of oxygen consumption rates and diffusion coefficients in multicellular spheroids.

W Mueller-Klieser
PMCID: PMC1434957  PMID: 6487734

Abstract

A method has been developed for the quantitative evaluation of oxygen tension (PO2) distributions in multicellular spheroids measured with O2-sensitive microelectrodes. The experimental data showed that multicellular tumor spheroids in stirred growth media were characterized by a diffusion-depleted zone surrounding the spheroids. This zone was elicited by an unstirred layer of medium next to the spheroid leading to a continuous decrease in the PO2 values from the bulk medium towards the spheroid surface. Theoretical considerations demonstrate that the volume-related O2 consumption rate, Q, in the spheroids can be assessed by measuring the PO2 gradient in the diffusion-depleted zone outside the spheroids. Accordingly, Krogh's diffusion constant, KS, in the spheroids can be determined through measuring the PO2 gradient within the spheroids. The results obtained suggest that multicellular spheroids represent useful in vitro tumor models for the experimental and theoretical analysis of the interrelationship among O2 supply to tumor cells, O2 metabolism in tumors tissue, and the responsiveness of cancer cells to treatment.

Full text

PDF
343

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boag J. W. Oxygen diffusion in tumour capillary networks. Bibl Anat. 1977;(15 Pt 1):266–269. [PubMed] [Google Scholar]
  2. Burton A. C. Rate of growth of solid tumours as a problem of diffusion. Growth. 1966 Jun;30(2):157–176. [PubMed] [Google Scholar]
  3. Carlsson J., Stålnacke C. G., Acker H., Haji-Karim M., Nilsson S., Larsson B. The influence of oxygen on viability and proliferation in cellular spheroids. Int J Radiat Oncol Biol Phys. 1979 Nov-Dec;5(11-12):2011–2020. doi: 10.1016/0360-3016(79)90953-2. [DOI] [PubMed] [Google Scholar]
  4. Deakin A. S. Model for the growth of a solid in vitro tumor. Growth. 1975 Mar;39(1):159–165. [PubMed] [Google Scholar]
  5. Franko A. J., Sutherland R. M. Oxygen diffusion distance and development of necrosis in multicell spheroids. Radiat Res. 1979 Sep;79(3):439–453. [PubMed] [Google Scholar]
  6. Freyer J. P., Sutherland R. M. Selective dissociation and characterization of cells from different regions of multicell tumor spheroids. Cancer Res. 1980 Nov;40(11):3956–3965. [PubMed] [Google Scholar]
  7. Grote J., Süsskind R., Vaupel P. Oxygen diffusivity in tumor tissue (DS-carcinosarcoma) under temperature conditions within the range of 20--40 degrees C. Pflugers Arch. 1977 Nov 25;372(1):37–42. doi: 10.1007/BF00582204. [DOI] [PubMed] [Google Scholar]
  8. Kaufman N., Bicher H. I., Hetzel F. W., Brown M. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids. Cancer Clin Trials. 1981;4(2):199–204. [PubMed] [Google Scholar]
  9. Mueller-Klieser W. F., Sutherland R. M. Influence of convection in the growth medium on oxygen tensions in multicellular tumor spheroids. Cancer Res. 1982 Jan;42(1):237–242. [PubMed] [Google Scholar]
  10. Mueller-Klieser W. F., Sutherland R. M. Oxygen tensions in multicell spheroids of two cell lines. Br J Cancer. 1982 Feb;45(2):256–264. doi: 10.1038/bjc.1982.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mueller-Klieser W., Freyer J. P., Sutherland R. M. Evidence for a major role of glucose in controlling development of necrosis in EMT6/Ro multicell tumor spheroids. Adv Exp Med Biol. 1983;159:487–495. doi: 10.1007/978-1-4684-7790-0_42. [DOI] [PubMed] [Google Scholar]
  12. Mueller-Klieser W., Sutherland R. M. Frequency distribution histograms of oxygen tensions in multicell spheroids. Adv Exp Med Biol. 1983;159:497–508. doi: 10.1007/978-1-4684-7790-0_43. [DOI] [PubMed] [Google Scholar]
  13. Rockwell S. C., Kallman R. F., Fajardo L. F. Characteristics of a serially transplanted mouse mammary tumor and its tissue-culture-adapted derivative. J Natl Cancer Inst. 1972 Sep;49(3):735–749. [PubMed] [Google Scholar]
  14. Sutherland R. M., Durand R. E. Radiation response of multicell spheroids--an in vitro tumour model. Curr Top Radiat Res Q. 1976 Jan;11(1):87–139. [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES