Oxygen Consumption and Oxygen Diffusion Properties of Multicellular Spheroids from two Different Cell Lines
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.
KeywordsOxygen Tension Multicellular Spheroid Multicellular Tumor Spheroid Cell Cycle State Spheroid Growth
Unable to display preview. Download preview PDF.
- Boag, J. W., 1969, Oxygen diffusion and oxygen depletion problems in radiobiology, Curr. Top. Radiat. Res., 5:141.Google Scholar
- 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
- 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
- Mueller-Klieser, W., 1983, Theoretical analysis of stationary oxygen tension profiles in multicell spheroids, Naunyn-Schmiedeberg’s Arch. Pharmacol., 322:R50.Google Scholar
- Mueller-Klieser, W., submitted, A method for the quantitative evaluation of oxygen tension distributions in multicellular spheroids, Biophys. J., (submitted).Google Scholar
- Rashevsky, N., 1960, “Mathematical Biophysics”, Dover Publications, Inc., New York.Google Scholar
- Sutherland, R. M., and Durand, Radiation response of multicellular spheroids — an in vitro tumour model, Curr. Top. Radia. Res., 11:87.Google Scholar
- 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