This paper provides a unified mathematical analysis of a family of non-local diffuse interface models for tumor growth describing evolutions driven by long-range interactions. These integro-partial differential equations model cell-to-cell adhesion by a non-local term and may be seen as non-local variants of the corresponding local model proposed by H. Garcke et al. (2016). The model in consideration couples a non-local Cahn-Hilliard equation for the tumor phase variable with a reaction-diffusion equation for the nutrient concentration, and takes into account also significant mechanisms such as chemotaxis and active transport. The system depends on two relaxation parameters: a viscosity coefficient and parabolic-regularization coefficient on the chemical potential. The first part of the paper is devoted to the analysis of the system with both regularizations. Here, a rich spectrum of results is presented. Weak well-posedness is first addressed, also including singular potentials. Then, under suitable conditions, existence of strong solutions enjoying the separation property is proved. This allows also to obtain a refined stability estimate with respect to the data, including both chemotaxis and active transport. The second part of the paper is devoted to the study of the asymptotic behavior of the system as the relaxation parameters vanish. The asymptotics are analyzed when the parameters approach zero both separately and jointly, and exact error estimates are obtained. As a by-product, well-posedness of the corresponding limit systems is established.
A considerable number of research works has been devoted to the study of tumor models. Several biophysical factors, such as cell proliferation, apoptosis, chemotaxis, angiogenesis and necrosis, have been discovered to have an impact on the complicated biological system of tumors. An indicator of the aggressiveness of tumor development is the instability of the shape of the tumor boundary. Complex patterns of tumor morphology have been explored by Lu, Min-Jhe et al. [Nonlinear simulation of vascular tumor growth with chemotaxis and the control of necrosis, Journal of Computational Physics 459 (…
Mathematical models that describe the tumor growth process have been formulated by several authors in order to understand how cancer develops and to develop new treatment approaches. In this study, it is aimed to investigate the long-time behavior of the two-phase diffuse-interface model, which was proposed in [11] to model a tumor tissue as a mixture of cancerous and healthy cells. Up to now, studies on the long-time behavior of this model have neglected chemotaxis and active transport, which have a significant effect on tumor growth. In this research, our main aim is to study this model with…
In this work, we study the Neumann initial boundary value problem for a three-component chemotaxis model in any dimensional bounded and smooth domains; this model is used to describe the branching of capillary sprouts during angiogenesis. First, we find three qualitatively simple sufficient conditions for qualitative global boundedness, and then, we establish two types of global stability for bounded solutions in qualitative ways. As a consequence of our findings, the underlying system without chemotaxis and the effect of ECs mitosis can not give rise to pattern formations. Our findings quanti…
A distributed optimal control problem for an extended model of phase field type for tumor growth is addressed. In this model, the chemotaxis effects are also taken into account. The control is realized by two control variables that design the dispensation of some drugs to the patient. The cost functional is of tracking type, whereas the potential setting has been kept quite general in order to allow regular and singular potentials to be considered. In this direction, some relaxation terms have been introduced in the system. We show the well-posedness of the state system, the Fréchet differenti…
We consider a simplified chemotaxis model of tumor angiogenesis, described by a Keller-Segel system on the two dimensional infinite cylindrical domain $(x, y) \in \mathbb{R} \times {\mathbf S^λ}$, where $ \mathbf S^λ$ is the circle of perimeter $λ>0$. The domain models a virtual channel where newly generated blood vessels toward the vascular endothelial growth factor will be located. The system is known to allow planar traveling wave solutions of an invading type. In this paper, we establish the nonlinear stability of these traveling invading waves when chemical diffusion is present if $λ$ is …
We investigate a multiphase Cahn-Hilliard model for tumor growth with general source terms. The multiphase approach allows us to consider multiple cell types and multiple chemical species (oxygen and/or nutrients) that are consumed by the tumor. Compared to classical two-phase tumor growth models, the multiphase model can be used to describe a stratified tumor exhibiting several layers of tissue (e.g., proliferating, quiescent and necrotic tissue) more precisely. Our model consists of a convective Cahn-Hilliard type equation to describe the tumor evolution, a velocity equation for the associat…
We revisit the following chemotaxis system modeling tumor invasion \begin{equation*} \begin{cases} u_t=Δu-\nabla \cdot(u\nabla v),& x\inΩ, t>0,\\ v_t=Δv+wz,& x\inΩ, t>0,\\ w_t=-wz,& x\inΩ, t>0,\\ z_t=Δz-z+u, & x\inΩ, t>0,\\ \end{cases} \end{equation*} in a smooth bounded domain $Ω\subset \mathbb{R}^n(n\geq 1)$ with homogeneous Neumann boundary and initial conditions. This model was recently proposed by Fujie et al. \cite{FIY14} as a model for tumor invasion with the role of extracellular matrix incorporated, and was analyzed by Fujie et al. \cite{FIWY16}, showing the uniform boundedness and co…
This paper studies the following system of differential equations modeling tumor angiogenesis in a bounded smooth domain $Ω\subset \mathbb{R}^N$ ($N=1,2$): $$\label{0} \left\{\begin{array}{ll} p_t=Δp-\nabla\cdotp p(\displaystyle\frac α{1+c}\nabla c+ρ\nabla w)+λp(1-p),\,& x\in Ω, t>0, c_t=Δc-c-μpc,\, &x\in Ω, t>0,\\ w_t= γp(1-w),\,& x\in Ω, t>0, \end{array}\right. $$ where $α, ρ, λ, μ$ and $γ$ are positive parameters. For any reasonably regular initial data $(p_0, c_0, w_0)$, we prove the global boundedness ($L^\infty$-norm) of $p$ via an iterative method. Furthermore, we investigate the long-t…
We consider a diffuse interface model for tumor growth consisting of a Cahn--Hilliard equation with source terms coupled to a reaction-diffusion equation, which models a tumor growing in the presence of a nutrient species and surrounded by healthy tissue. The well-posedness of the system equipped with Neumann boundary conditions was found to require regular potentials with quadratic growth. In this work, Dirichlet boundary conditions are considered, and we establish the well-posedness of the system for regular potentials with higher polynomial growth and also for singular potentials. New diffi…
New estimates and global existence results are provided for a class of systems of cross diffusion equations arising from the modeling of chemotaxis with local sensing, possibly featuring a growth term of logistic-type as well. For sublinear non-increasing motility functions, convergence to the spatially homogeneous steady state is shown, a dedicated Lyapunov functional being constructed for that purpose.
This paper is concerned with the well-posedness and large-time behavior of a two dimensional PDE-ODE hybrid chemotaxis system describing the initiation of tumor angiogenesis. We first transform the system via a Cole-Hopf type transformation into a parabolic-hyperbolic system and show that the solution of the transformed system converges to a constant equilibrium state as time tends to infinity. Finally we reverse the Cole-Hopf transformation and obtain the relevant results for the pre-transformed PDE-ODE hybrid system. In contrast to the existing related results, where continuous initial datum…
The hydrodynamic limit of a one dimensional kinetic model describing chemotaxis is investigated. The limit system is a conservation law coupled to an elliptic problem for which the macroscopic velocity is possibly discontinuous. Therefore, we need to work with measure-valued densities. After recalling a blow-up result in finite time of regular solutions for the hydrodynamic model, we establish a convergence result of the solutions of the kinetic model towards solutions of a problem limit defined thanks to the flux. Numerical simulations illustrate this convergence result.
Does indirectness of signal production reduce the explosion-supporting potential in chemotaxis-haptotaxis systems? Global classical solvability in a class of models for cancer invasion (and more)
We consider a chemotaxis-fluid system involving nonlinear cell diffusion of porous medium type, signal consumption by cells, and rather general, possibly matrix-valued, chemotactic sensitivities. It is shown that if the corresponding diffusion exponent $m$ satisfies $m>7/6$, then for all reasonably regaular initial data an associated initial-boundary value problem in smoothly bounded three-dimensional domains possesses a globally defined weak solution which is bounded. Under a mild additional assumption on the signal consumption rate, it is moreover shown that any nontrivial of these solutions…
We present and analyze new multi-species phase-field mathematical models of tumor growth and ECM invasion. The local and nonlocal mathematical models describe the evolution of volume fractions of tumor cells, viable cells (proliferative and hypoxic cells), necrotic cells, and the evolution of MDE and ECM, together with chemotaxis, haptotaxis, apoptosis, nutrient distribution, and cell-to-matrix adhesion. We provide a rigorous proof of the existence of solutions of the coupled system with gradient-based and adhesion-based haptotaxis effects. In addition, we discuss finite element discretization…
In this work we analyse a PDE-ODE problem modelling the evolution of a Glioblastoma, which includes chemotaxis term directed to vasculature. First, we obtain some a priori estimates for the (possible) solutions of the model. In particular, under some conditions on the parameters, we obtain that the system does not develop blow-up at finite time. In addition, we design a fully discrete finite element scheme for the model which preserves some pointwise estimates of the continuous problem. Later, we make an adimensional study in order to reduce the number of parameters. Finally, we detect the mai…
This manuscript deals with the three-dimensional version of a flux-limited Keller-Segel system coupled to the incompressible Stokes equations through transport and buoyancy. The main goal consists in verifying that within a certain parameter regime, known as being optimal therefor in some fluid-free simplification, a feature of blow-up prevention by suitably strong flux limitation persists also in the framework of the considered full chemotaxis-fluid system. To achieve this, as a secondary objective of possibly independent interest the manuscript separately establishes some conditional bounds …
We provide a short review of existing models with multiple taxis performed by (at least) one species and consider a new mathematical model for tumor invasion featuring two mutually exclusive cell phenotypes (migrating and proliferating). The migrating cells perform nonlinear diffusion and two types of taxis in response to non-diffusing cues: away from proliferating cells and up the gradient of surrounding tissue. Transitions between the two cell subpopulations are influenced by subcellular (receptor binding) dynamics, thus conferring the setting a multiscale character. We prove global existenc…
A chemotaxis system possibly containing rotational components of the cross-diffusive flux is studied under no-flux boundary conditions in a bounded domain $Ω\subset R^n$, $n\ge 1$, with smooth boundary, where the evolution of the signal is determined by consumption through cells. In contrast to related Keller-Segel-type problems with scalar sensitivities, in presence of such tensor-valued sensitivities this system in general apparently does not possess any useful gradient-like structure. Accordingly, its analysis needs to be based on new types of a priori bounds. Using a spatio-temporal $L^2$ …
Chemotaxis is the process by which cells behave in a way that follows the chemical gradient. Applications to bacteria growth, tissue inflammation, and vascular tumors provide a focus on optimization strategies. Experiments can characterize the form of possible chemotactic sensitivities. This paper addresses the recovery of the chemotactic sensitivity from these experiments while allowing for nonlinear dependence of the parameter on the state variables. The existence of solutions to the forward problem is analyzed. The identification of a chemotactic parameter is determined by inverse problem t…
This paper concerns multiphase models of tumor growth in interaction with a surrounding tissue, taking into account also the interplay with diffusible nutrients feeding the cells. Models specialize in nonlinear systems of possibly degenerate parabolic equations, which include phenomenological terms related to specific cell functions. The paper discusses general modeling guidelines for such terms, as well as for initial and boundary conditions, aiming at both biological consistency and mathematical robustness of the resulting problems. Particularly, it addresses some qualitative properties such…
We consider a rather general class of evolutionary PDEs involving dissipation (of possibly fractional order), which competes with quadratic nonlinearities on the regularity of the overall equation. This includes as prototype models, Burgers' equation, the Navier-Stokes equations, the surface quasi-geostrophic equations and the Keller-Segel model for chemotaxis. Here we establish a Petrowsky type parabolic estimate of such equations which entail a precise time decay of higher-order Sobolev norms for this class of equations. To this end, we introduce as a main new tool, an "infinite order energy…
We present a mathematical model describing the time development of a population of tumors subject to mutual angiogenic inhibitory signaling. Based on biophysical derivations, it describes organism-scale population dynamics under the influence of three processes: birth (dissemination of secondary tumors), growth and inhibition (through angiogenesis). The resulting model is a nonlinear partial differential transport equation with nonlocal boundary condition. The nonlinearity stands in the velocity through a nonlocal quantity of the model (the total metastatic volume). The asymptotic behavior of …
We study the McKean-Vlasov equation \[ \partial_t \varrho= β^{-1} Δ\varrho + κ\nabla \cdot (\varrho \nabla (W \star \varrho)) \, , \] with periodic boundary conditions on the torus. We first study the global asymptotic stability of the homogeneous steady state. We then focus our attention on the stationary system, and prove the existence of nontrivial solutions branching from the homogeneous steady state, through possibly infinitely many bifurcations, under appropriate assumptions on the interaction potential. We also provide sufficient conditions for the existence of continuous and discontinu…
