A model for the growth of multicellular spheroids

Abstract. Based on biological observations and the basic physical properties of tri‐dimensional structures, a mathematical expression is derived to relate the growth rate of multicellular spheroids to some easily measurable parameters. This model involves properties both of the individual cells and of the spheroid structure, such as the cell doubling time in monolayer, the rate of cell shedding from the spheroid and the depth of the external rim of cycling cells. The derived growth equation predicts a linear expansion of the spheroid diameter with time. The calculated growth rate for a number of spheroid cell types is in good agreement with experimental data. The model provides a simple and practical view of growth control in spheroids, and is further adapted to include parameters presumably responsible for the growth saturation in large spheroids.

[1]  J. Carlsson,et al.  Proliferation and viability in cellular spheroids of human origin. , 1978, Cancer research.

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

[3]  Burton Ac,et al.  Rate of growth of solid tumours as a problem of diffusion. , 1966, Growth.

[4]  J P Freyer,et al.  Shedding of mitotic cells from the surface of multicell spheroids during growth , 1981, Journal of cellular physiology.

[5]  J. Folkman,et al.  SELF-REGULATION OF GROWTH IN THREE DIMENSIONS , 1973, The Journal of experimental medicine.

[6]  A C Burton,et al.  Rate of growth of solid tumours as a problem of diffusion. , 1966, Growth.

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

[8]  J. Yuhas,et al.  Growth fraction as the major determinant of multicellular tumor spheroid growth rates. , 1978, Cancer research.

[9]  J. Folkman,et al.  Influence of geometry on control of cell growth. , 1975, Biochimica et biophysica acta.

[10]  M. Tubiana The kinetics of tumour cell proliferation and radiotherapy. , 1971, The British journal of radiology.

[11]  R E Durand,et al.  CELL CYCLE KINETICS IN AN IN VITRO TUMOR MODEL , 1976, Cell and tissue kinetics.

[12]  R. Shymko,et al.  Cellular and geometric control of tissue growth and mitotic instability. , 1976, Journal of theoretical biology.

[13]  Inch Wr,et al.  Growth of nodular carcinomas in rodents compared with multi-cell spheroids in tissue culture. , 1970 .

[14]  Shymko Rm,et al.  Cellular and geometric control of tissue growth and mitotic instability. , 1976 .

[15]  P. J. Ponzo,et al.  A model for the growth of a solid tumor with non-uniform oxygen consumption , 1977 .

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

[17]  H. Greenspan Models for the Growth of a Solid Tumor by Diffusion , 1972 .

[18]  J. Yuhas,et al.  Multicellular tumor spheroid formation by breast cancer cells isolated from different sites. , 1978, Cancer research.