Skip to main content
Log in

Diffusion regulated growth characteristics of a spherical prevascular carcinoma

  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Recently a mathematical model of the prevascular phases of tumor growth by diffusion has been investigated (S. A. Maggelakis and J. A. Adam,Math. Comput. Modeling, in press). In this paper we examine in detail the results and implications of that mathematical model, particularly in the light of recent experimental work carried out on multicellular spheroids. The overall growth characteristics are determined in the present model by four parameters:Q, γ, b, andδ, which depend on information about inhibitor production rates, oxygen consumption rates, volume loss and cell proliferation rates, and measures of the degree of non-uniformity of the various diffusion processes that take place. The integro-differential growth equation is solved for the outer spheroid radiusR 0(t) and three related inner radii subject to the solution of the governing time-independent diffusion equations (under conditions of diffusive equilibrium) and the appropriate boundary conditions. Hopefully, future experimental work will enable reasonable bounds to be placed on parameter values referred to in this model: meanwhile, specific experimentally-provided initial data can be used to predict subsequent growth characteristics ofin vitro multicellular spheroids. This will be one objective of future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literature

  • Adam, J. A. 1986. A simplified mathematical model of tumor growth.Math. Biosci. 81, 224–229.

    Article  Google Scholar 

  • Adam, J. A. 1987. A mathematical model of tumor growth. II. Effects of geometry and spatial nonuniformity on stability.Math. Biosci. 86, 183–211.

    Article  MATH  Google Scholar 

  • Adam, J. A. 1987. A mathematical model of tumor growth. III. Comparison with experiment.Math. Biosci. 86, 213–227.

    Article  MATH  Google Scholar 

  • Adam, J. A. 1989. Corrigendum. A mathematical model of tumor growth by diffusion.Math. Biosci. 94, 155.

    Article  MathSciNet  Google Scholar 

  • Adam, J. A. and S. A. Maggelakis. 1989. Mathematical models of tumor growth. IV. Effects of a necrotic core.Math. Biosci.,97, 121–134.

    Article  MATH  Google Scholar 

  • Anderson, N. and A. M. Arthurs. 1980. Complementary variational principles for diffusion problems with Michaelis-Menten kinetics.Bull. math. Biol. 42, 131–135.

    Article  MATH  Google Scholar 

  • Arve, B. H. and A. I. Liapis. 1988. Oxygen tension in tumors predicted by a diffusion with absorption model involving a moving free boundary.Math. Comput. Modeling 10, 159–174.

    Article  MATH  Google Scholar 

  • Do, D. D. and P. F. Greenfield. 1981. A finite integral transform technique for solving the diffusion-reaction equations with Michaelis-Menten kinetics.Math. Biosci. 54, 31–47.

    Article  MATH  MathSciNet  Google Scholar 

  • Folkman, J. 1974. Tumor angiogenesis.Adv. Cancer Res. 19, 331–338.

    Google Scholar 

  • Folkman J. and M. Hochberg. 1973. Self-regulation of growth in three dimensions.J. Exp. Med. 138, 745–753.

    Article  Google Scholar 

  • Folkman, J. and M. Klagsbrun. 1987. Angiogenic factors.Science 235, 442–447.

    Google Scholar 

  • Franko, A. J. and H. I. Freedman. 1984. Model of diffusion on oxygen to spheroids grown in stationary medium—I. Complete spherical symmetry.Bull. math. Biol. 46, 205–217.

    Article  MATH  Google Scholar 

  • Franko, A. J. and R. M. Sutherland. 1979. Oxygen diffusion distance and the development of necrosis in multicell spheroids.Radiat. Res. 79, 439–453.

    Google Scholar 

  • Franko, A. J. and R. M. Sutherland. 1979. Radiation survival of cells from spheroids grown in different oxygen concentrations.Radiat. Res. 79, 454–467.

    Google Scholar 

  • Freyer, J. P. and R. M. Sutherland. 1983. Determination of diffusion constants for metabolites in multicell tumor spheroids. In:Oxygen Transport to Tissue—IV, pp., 463–475. New York: Plenum.

    Google Scholar 

  • Freyer, J. P., E. Tustanoff, A. J. Franko and R. M. Sutherland. 1984.In situ oxygen consumption rates of cells in V-79 multicellular spheroids during growth.J. Cell Physiol. 118, 53–61.

    Article  Google Scholar 

  • Goldacre, R. J. and G. Sylven. 1962. On the access of blood-borne dyes to various tumor regions.Br. J. Cancer 16, 306.

    Google Scholar 

  • Greenspan, H. P. 1972. Models for the growth of a solid tumor by diffusion.Stud. appl. Math. 52, 317–340.

    Google Scholar 

  • Greenspan, H. P. 1974. On the self-inhibited growth of cell cultures.Growth 38, 81–95.

    Google Scholar 

  • Grossman, U. 1984. Profiles of oxygen partial pressure and oxygen consumption inside multicellular spheroids.Recent Results Cancer Res. 95, 150–161.

    Google Scholar 

  • Hiltman, P. and P. Lory. 1983. On oxygen diffusion in a spherical cell with Michaelis-Menten oxygen uptake kinetics.Bull. math. Biol. 45, 661–664.

    Article  Google Scholar 

  • Jain, R. K. and J. Wei. 1977. Dynamics of drug transport in solid tumors: distributed parameter model.J. Bioengng 1, 313–330.

    Google Scholar 

  • King, W. E., D. S. Schultz and R. A. Gatenby. 1986. Multi-region models for describing oxygen tension profiles in human tumors.Chem. Engng Commun. 47, 73–91.

    Google Scholar 

  • King, W. E., D. S. Schultz and R. A. Gatenby. 1988. An analysis of systematic tumor oxygenation using multi-region models.Chem. Engng Commun. 64, 137–153.

    Google Scholar 

  • Laird, A. K. 1975. Dynamics of tumor growth. Comparisons of growth rates and extrapolation of growth curve to one cell.Br. J. Cancer 19, 278.

    Google Scholar 

  • Landry, J., J. P. Freyer and R. M. Sutherland. 1982. A model for the growth of multicellular spheroids.Cell Tissue Kinet. 15, 585–594.

    Google Scholar 

  • Liapis, A. I., G. G. Lipscomb and O. K. Crosser. 1982. A model of oxygen diffusion in absorbing tissue.Math. Modeling 3, 83–92.

    Article  MATH  MathSciNet  Google Scholar 

  • Lin, S. H. 1976. Oxygen diffusion in a spherical cell with nonlinear oxygen uptake kinetics.J. theor. Biol. 60, 449–457.

    Article  Google Scholar 

  • Lin, S. H. 1979. Nonlinear diffusion in biological systems.Bull. math. Biol. 41, 151–162.

    Article  MATH  MathSciNet  Google Scholar 

  • Maggelakis, S. A. and J. A. Adam. 1989. Mathematical model of prevascular growth of a spherical carcinoma.Math. Comput. Modeling, in press.

  • Maggelakis, S. A. and J. A. Adam. 1989. Note on a class of nonlinear time independent diffusion equations.Appl. Math. Lett. 2, 141–145.

    Article  MATH  MathSciNet  Google Scholar 

  • McElwain, D. L. S. 1978. A re-examination of oxygen diffusion in a spherical cell with Michaelis-Menten oxygen uptake kinetics.J. theor. Biol. 71, 255–263.

    Article  Google Scholar 

  • McElwain, D. L. S. 1981. A comment on Lin's paper on nonlinear diffusion in biological systems.Bull. math. Biol. 43, 117–120.

    Article  MATH  MathSciNet  Google Scholar 

  • McElwain, D. L. S. and P. J. Ponzo. 1977. A model for the growth of solid tumor with nonuniform oxygen consumption.Math. Biosci. 35, 267–279.

    Article  MATH  Google Scholar 

  • McElwain, D. L. S., R. Callcott and L. E. Morris. 1979. A model of vascular compression in solid tumors.J. theor. Biol. 78, 405–415.

    Article  Google Scholar 

  • Mueller-Klieser, W. F. 1984. Method for the determination of oxygen consumption rates and diffusion coefficients in multicellular spheroids.Biophys. J. 46, 343–348.

    Article  Google Scholar 

  • Mueller-Klieser, W. F. and R. M. Sutherland. 1982. Oxygen tensions in multicell spheroids of two cell lines.Br. J. Cancer 45, 256–263.

    Google Scholar 

  • Mueller-Klieser, W. F. and R. M. Sutherland. 1984. Oxygen consumption and oxygen diffusion properties of multicellular spheroids from two different cell lines.Adv. exp. Med. Biol., in press.

  • Mueller-Klieser, W. F., J. P. Freyer and R. M. Sutherland. 1983. Evidence for a major role of glucose in controlling development of necrosis in EMT6/R0 multicell tumor spheroids. In:Oxygen Transport to Tissue—IV, pp. 487–495. New York: Plenum.

    Google Scholar 

  • Schultz, D. S. and W. E. King. 1987. On the analysis of oxygen diffusion in biological systems.Math. Biosci. 83, 179–190.

    Article  MATH  Google Scholar 

  • Shymko, R. M. and L. Glass. 1976. Cellular and geometric control of tissue growth and mitotic instability.J. theor. Biol. 63, 355–374.

    Article  Google Scholar 

  • Sutherland, R. M. 1988. Cell and environment interactions in tumor microregions: the multicell spheroid model.Science 240, 177–184.

    Google Scholar 

  • Sutherland, R. M. and R. E. Durand. 1976. Radiation response of multicellular spheroids—anin vitro tumor model.Curr. Top. Radiat. res. 11, 87–139.

    Google Scholar 

  • Swan, G. W. 1981. Optimization of human cancer radiotherapy.Lecture Notes in Biomathematics, Vol. 42. Berlin: Springer.

    Google Scholar 

  • Tannock, I. 1976. Oxygen distribution in tumours: influence on cell proliferation and implications for tumour therapy.Adv. exp. Med. Biol. 75, 597–603.

    Google Scholar 

  • Tannock, I. F. 1968. The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumor.Br. J. Cancer 22, 258–273.

    Google Scholar 

  • Thews, G. and P. Vaupel. 1976. Oxygen supply conditions in tumor tissuein vivo.Adv. exp. Med. Biol. 75, 537–546.

    Google Scholar 

  • Tosaka, N. and S. Miyaka. 1982. Analysis of a nonlinear diffusion problem with Michaelis-Menten kinetics by an integral equation method.Bull. math. Biol. 44, 841–849.

    Article  MATH  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adam, J.A., Maggelakis, S.A. Diffusion regulated growth characteristics of a spherical prevascular carcinoma. Bltn Mathcal Biology 52, 549–582 (1990). https://doi.org/10.1007/BF02462267

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02462267

Keywords

Navigation