Mass concentration in a nonlocal model of clonal selection

被引:19
作者
Busse, J. -E. [1 ]
Gwiazda, P. [2 ,3 ]
Marciniak-Czochra, A. [1 ,4 ,5 ]
机构
[1] Heidelberg Univ, BIOQUANT, Inst Appl Math, Neuenheimer Feld 294, D-69120 Heidelberg, Germany
[2] Univ Warsaw, Inst Appl Math & Mech, Ul Banacha 2, PL-02097 Warsaw, Poland
[3] Polish Acad Sci, Inst Math, Sniadeckich 8, PL-00656 Warsaw, Poland
[4] Heidelberg Univ, Interdisciplinary Ctr Sci Comp IWR, Neuenheimer Feld 205, D-69120 Heidelberg, Germany
[5] Heidelberg Univ, Bioquant, Neuenheimer Feld 205, D-69120 Heidelberg, Germany
关键词
Integro-differential equations; Mass concentration; Lyapunov function; Selection process; Clonal evolution; Cell differentiation model; Bounded Lipschitz distance; ACUTE MYELOID-LEUKEMIA; CELL-DIVISION; SELF-RENEWAL; DYNAMICS; EVOLUTION; CONVERGENCE; EQUATIONS; HIERARCHY; SURVIVAL; RELAPSE;
D O I
10.1007/s00285-016-0979-3
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Self-renewal is a constitutive property of stem cells. Testing the cancer stem cell hypothesis requires investigation of the impact of self-renewal on cancer expansion. To better understand this impact, we propose a mathematical model describing the dynamics of a continuum of cell clones structured by the self-renewal potential. The model is an extension of the finite multi-compartment models of interactions between normal and cancer cells in acute leukemias. It takes a form of a system of integro-differential equations with a nonlinear and nonlocal coupling which describes regulatory feedback loops of cell proliferation and differentiation. We show that this coupling leads to mass concentration in points corresponding to the maxima of the self-renewal potential and the solutions of the model tend asymptotically to Dirac measures multiplied by positive constants. Furthermore, using a Lyapunov function constructed for the finite dimensional counterpart of the model, we prove that the total mass of the solution converges to a globally stable equilibrium. Additionally, we show stability of the model in the space of positive Radon measures equipped with the flat metric (bounded Lipschitz distance). Analytical results are illustrated by numerical simulations.
引用
收藏
页码:1001 / 1033
页数:33
相关论文
共 56 条
[1]  
Ackleh AS, 2005, DISCRETE CONT DYN-B, V5, P917
[2]   Survival of the fittest in a generalized logistic model [J].
Ackleh, AS ;
Marshall, DF ;
Heatherly, HE ;
Fitzpatrick, BG .
MATHEMATICAL MODELS & METHODS IN APPLIED SCIENCES, 1999, 9 (09) :1379-1391
[3]  
Ambrosio L., 2000, OX MATH M, pxviii, DOI [10.1017/S0024609301309281, 10.1093/oso/9780198502456.001.0001]
[4]  
[Anonymous], 1973, RADON MEASURES
[5]   Multiparametric bifurcation analysis of a basic two-stage population model [J].
Baer, S. M. ;
Kooi, B. W. ;
Kuznetsov, Yu. A. ;
Thieme, H. R. .
SIAM JOURNAL ON APPLIED MATHEMATICS, 2006, 66 (04) :1339-1365
[6]  
Barles G, 2009, METHODS APPL ANAL, V16, P321
[7]   Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[8]   Stationary distributions under mutation-selection balance: Structure and properties [J].
Burger, R ;
Bomze, IM .
ADVANCES IN APPLIED PROBABILITY, 1996, 28 (01) :227-251
[9]  
Burger R., 2000, MATH THEORY SELECTIO, V228
[10]   Stationary solutions of a selection mutation model: The pure mutation case [J].
Calsina, A ;
Cuadrado, S .
MATHEMATICAL MODELS & METHODS IN APPLIED SCIENCES, 2005, 15 (07) :1091-1117