Influence of convection in the growth medium on oxygen tensions in multicellular tumor spheroids.

Abstract Recessed microelectrodes have been used to measure oxygen tensions ( P O 2 ) in tumor spheroids of EMT6/Ro cells which were grown in spinner flasks. For the P O 2 measurements, the spheroids were put into a thermostatically controlled measuring chamber that was designed to create conditions similar to those to which the spheroids are exposed in spinner flasks. Under these conditions, different electrode tracks yielded highly reproducible, symmetrical P O 2 profiles in ideally spherical spheroids. Asymmetrically shaped spheroids exhibited asymmetries in their P O 2 profiles. The P O 2 profiles are characterized by a diffusion-depleted zone at the spheroid surface, a steep decrease within 200 to 250 μm from the rim, and a plateau in the central part of spheroids larger than 500 μm. It was determined that the P O 2 profiles may be influenced by the flow velocity of the surrounding medium, particularly if the uniform diffusion of oxygen from the bulk of the growth medium to the spheroids is impaired. It is concluded that considerable differences in oxygenation are to be expected between spheroids grown in spinner flasks and spheroids grown in static media.

[1]  J. Carlsson,et al.  The fine structure of three-dimensional colonies of human glioma cells in agarose culture. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[2]  Deakin As,et al.  Model for the growth of a solid in vitro tumor. , 1975 .

[3]  Lübbers Dw.  Methods of measuring oxygen tensions of blood and organ surfaces. , 1966 .

[4]  T. K. Goldstick,et al.  Oxygen electrode design criteria and performance characteristics: recessed cathode. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[5]  R. Sutherland,et al.  Hypoxic cells in an in vitro tumour model. , 1973, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[6]  R. Sutherland,et al.  Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. , 1971, Journal of the National Cancer Institute.

[7]  P. Nair,et al.  A microelectrode for measuring intracellular pH. , 1967, Advances in experimental medicine and biology.

[8]  J. Boag.  OXYGEN DIFFUSION AND OXYGEN DEPLETION PROBLEMS IN RADIOBIOLOGY. , 1969 .

[9]  P. Nair,et al.  Intracellular Po2 and Its Regulation in Resting Skeletal Muscle of the Guinea Pig , 1967, Circulation research.

[10]  P Vaupel,et al.  Effects of hyperthermia on normal and tumor microenvironment. , 1980, Radiology.

[11]  P. Vaupel.  Hypoxia in neoplastic tissue. , 1977, Microvascular research.

[12]  J. Carlsson,et al.  Plasma Membrane Motility and Proliferation of Human Glioma Cells In Agarose and Monolayer Cultures , 1978, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[13]  C. Koch,et al.  Plateau phase in growth induced by hypoxia. , 1973, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[14]  R. Sutherland,et al.  Oxygen diffusion distance and development of necrosis in multicell spheroids. , 1979, Radiation research.

[15]  R. Sutherland,et al.  Radiation response of multicell spheroids--an in vitro tumour model. , 1976, Current topics in radiation research quarterly.

[16]  A S Deakin,et al.  Model for the growth of a solid in vitro tumor. , 1975, Growth.

[17]  I. Silver.  Problems in the Investigation of Tissue Oxygen Microenvironment , 1973 .

[18]  J P Freyer,et al.  Selective dissociation and characterization of cells from different regions of multicell tumor spheroids. , 1980, Cancer research.

[19]  J. Carlsson,et al.  A proliferation gradient in three‐dimensional colonies of cultured human glioma cells , 1977, International journal of cancer.

[20]  D. Lübbers.  Methods of measuring oxygen tensions of blood and organ surfaces. , 1966, International anesthesiology clinics.

[21]  R. Sutherland,et al.  Resistance to adriamycin in multicellular spheroids. , 1979, International journal of radiation oncology, biology, physics.

[22]  R. Sutherland,et al.  Radiation survival of cells from spheroids grown in different oxygen concentrations. , 1979, Radiation research.

[23]  R. Sutherland,et al.  Repair and reoxygenation following irradiation of an in vitro tumor model. , 1976, International journal of radiation oncology, biology, physics.

[24]  J. Carlsson,et al.  The influence of oxygen on viability and proliferation in cellular spheroids. , 1979, International journal of radiation oncology, biology, physics.