Multiscale mathematical modeling occurrence and growth of a tumour in an epithelial tissue

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1 : :57; MSC 21: 92D2.. 1,,.. 1,.. 2, 1 -,,, 61499,.,.,. 24 2,,, 32,. dmitribratsun@rambler.ru, pismen@technion.ac.il , - -, - -, -., , - -. :,,,,, Multiscale mathematical modeling occurrence and growth of a tumour in an epithelial tissue D. A. Bratsun 1, A. P. Zakharov 1, L.M. Pismen 2 1 Perm State Humanitarian Pedagogical University, 24 Sibirskaya str., Perm, 61499, Russia 2 Department of Chemical Engineering, Technion Israel Institute of Technology, 32 Haifa, Israel Abstract. In this paper we propose a mathematical model of cancer tumour occurrence in a quasi twodimensional epithelial tissue. Basic model of the epithelium growth describes the appearance of intensive movement and growth of tissue when it is damaged. The model includes the effects of division of cells and intercalation. It is assumed that the movement of cells is caused by the wave of mitogen-activated protein kinase (MAPK), which in turn activated by the chemo-mechanical signal propagating along tissue due to its local damage. In this paper it is assumed that cancer cells arise from local failure of spatial synchronization of circadian rhythms. The study of the evolutionary dynamics of the model could determine the chemo-physical properties of a tumour, and spatial relationship between the occurrence of cancer cells and development of the entire tissue parameters coordinating its evolution through the exchange of chemical and mechanical signals. Keywords: mathematical modeling, cancer growth, circadian rhythms, gene regulation, synchronization, complex systems Citation: Computer Research and Modeling, 214, vol. 6, no. 4, pp (Russian). ( -26/244), ( 31-) ( ). 214,,

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18 62..,..,.., 9, -,. - : A 3 3 / 2, 1.2, 1., l.4. T l. -,. -, - -.,. -, -, -.,,., (, ). - ( - - ). -.,,. -. -,, -, -..., Neurospora crassa // , ,.., // , ,.. // , ,.. //. 29. T. 1, ,..,..,.. // , ,..,.. - // C ,..,.. // ,

19 63....:, c. Alarcon T. A cellular automaton model for tumour growth in inhomogeneous environment // J. Theor. Biol. 23. V P Ambrosi D., Preziosi L. On the closure of mass balance models for tumour growth // Math. Mod. Meth. Appl. Sci. 22. Vol. 12. P Anderson A. A hybrid mathematical model of solid tumour invasion: The importance of cell adhesion // Math. Med. Biol. 25. Vol. 22. P Anderson A., eaver A., Cummings P., Quaranta V. Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment // Cell. 26. Vol P Bratsun D., Volfson D., Hasty J., Tsimring L. Delay-induced stochastic oscillations in gene regulation // PNAS. 25. Vol. 12, No. 41. P Byrne H. M., King J. R., McElwain D. L. S. A two-phase model of solid tumor growth // Appl. Math. Lett. 23. Vol. 16. P Dyson J., Villella-Bressan R., ebb G. The steady state of a maturity structured tumor cord cell population // Discr. Cont. Dyn. Syst. B. 24. Vol. 4. P Dunlap J. C. Molecular bases for circadian clocks // Cell Vol. 96, No. 2. P Greene M.. Circadian rhythms and tumor growth // Cancer Letters Vol P Gyllenberg M., ebb G. A nonlinear structured population model of tumour growth with quiescence // J. Math. Biol Vol. 28. P Honda H., Nagai T. and Tanemura M. Two different mechanisms of planar cell intercalation leading to tissue elongation // Developmental Dynamics. 28. Vol P riedl P., Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer // Nat. Rev. Mol. Cell Biol. 29. Vol. 1. P Kim Y., Stolarska M.A., Othmer H.G. A hybrid model for tumour spheroid growth in vitro I: Theoretical development and early results // Math. Mod. Meth. Appl. Sci. 27. Vol. 17. P Kimmel M., Lachowicz M., wierniak A. Cancer growth and progression, mathematical problems and computer simulations // Int. J. Appl. Math. Comput. Sci. 23. Vol. 13. P Komarova N. Stochastic modeling of loss- and gain-of-function mutation in cancer // Math. Mod. Meth. Appl. Sci. 27. V. 17. P Koseska A., Ullner E., Volkov E., Kurths J., Garcia-Ojalvo J. Cooperative differentiation through clustering in multicellular populations // J. Theor. Biol. 21. Vol P Matsubayashi Y., Ebisuya M., Honjoh S., and Nishida E. Erk activation propagates in epithelial cell sheets and regulates their migration during wound healing // Curr. Biol. 24. Vol. 14. P Nikolic D. L., Boettiger A. N., Bar-Sagi D., Carbeck J. D., and Shvartsman S. Y. Role of boundary conditions in an experimental model of epithelial wound healing // Am. J. Physiol. Cell Physiol. 26. Vol P Rossetti S., Esposito J., Corlazzoli., Gregorski A., Sacchi N. Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes // Cell Cycle Vol. 11. P Salm M., Pismen L.M. Chemical and mechanical signaling in epithelial spreading // Phys. Biol Vol. 9, N.2. P Smolen P., Baxter D. A., Byrne J. H. Reduced models of the circadian oscillators in Neurospora crassa and Drosophila melanogaster illustrate mechanistic similarities // OMICS. 23. Vol. 7, No. 4. P , 4,

20 64..,..,.. Smolle J., Stettner H. Computer simulation of tumour cell invasion by a stochastic growth model // J. Math. Biol Vol. 16. P Viktorinova I., Pismen L. M., Aigouy B., Dahmann C. The role of signal relay in collective cell polarization // J. R. Soc. Interface Vol. 8. P Vogelstein B., Kinzler K.. Cancer genes and the pathways they control // Nature Med. 24. Vol. 1. P ebb G.. Theory of Nonlinear Age-Dependent Population Dynamics. Marcel Dekker, 1985 P eber G.. Molecular Mechanisms of Cancer. Springer, 27. P. 645.

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