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Faculty / Organisational entity
SDE-driven modeling of phenotypically heterogeneous tumors: The influence of cancer cell stemness
(2018)
We deduce cell population models describing the evolution of a tumor (possibly interacting with its
environment of healthy cells) with the aid of differential equations. Thereby, different subpopulations
of cancer cells allow accounting for the tumor heterogeneity. In our settings these include cancer
stem cells known to be less sensitive to treatment and differentiated cancer cells having a higher
sensitivity towards chemo- and radiotherapy. Our approach relies on stochastic differential equations
in order to account for randomness in the system, arising e.g., by the therapy-induced decreasing
number of clonogens, which renders a pure deterministic model arguable. The equations are deduced
relying on transition probabilities characterizing innovations of the two cancer cell subpopulations,
and similarly extended to also account for the evolution of normal tissue. Several therapy approaches
are introduced and compared by way of tumor control probability (TCP) and uncomplicated tumor
control probability (UTCP). A PDE approach allows to assess the evolution of tumor and normal
tissue with respect to time and to cell population densities which can vary continuously in a given set
of states. Analytical approximations of solutions to the obtained PDE system are provided as well.
We propose a multiscale model for tumor cell migration in a tissue network. The system of equations involves a structured population model for the tumor cell density, which besides time and
position depends on a further variable characterizing the cellular state with respect to the amount
of receptors bound to soluble and insoluble ligands. Moreover, this equation features pH-taxis and
adhesion, along with an integral term describing proliferation conditioned by receptor binding. The
interaction of tumor cells with their surroundings calls for two more equations for the evolution of
tissue fibers and acidity (expressed via concentration of extracellular protons), respectively. The
resulting ODE-PDE system is highly nonlinear. We prove the global existence of a solution and
perform numerical simulations to illustrate its behavior, paying particular attention to the influence
of the supplementary structure and of the adhesion.
We investigate a PDE-ODE system describing cancer cell invasion in a tissue network. The model is an extension of the multiscale setting in [28,40], by considering two subpopulations of tumor cells interacting mutually and with the surrounding tissue. According to the go-or-grow hypothesis, these subpopulations consist of moving and proliferating cells, respectively. The mathematical setting also accommodates the effects of some therapy approaches. We prove the global existence of weak solutions to this model and perform numerical simulations to illustrate its behavior for different therapy strategies.
Starting from the two-scale model for pH-taxis of cancer cells introduced in [1], we consider here an extension accounting for tumor heterogeneity w.r.t. treatment sensitivity and a treatment approach including chemo- and radiotherapy. The effect of peritumoral region alkalinization on such therapeutic combination is investigated with the aid of numerical simulations.
We propose a model for acid-mediated tumor invasion involving two different scales: the microscopic one, for the dynamics of intracellular protons and their exchange with their extracellular counterparts, and the macroscopic scale of interactions between tumor cell and normal cell populations, along with the evolution of extracellular protons. We also account for the tactic behavior of cancer cells, the latter being assumed to biase their motion according to a gradient of extracellular protons (following [2,31] we call this pH taxis). A time dependent (and also time delayed) carrying capacity for the tumor cells in response to the effects of acidity is considered as well. The global well posedness of the resulting multiscale model is proved with a regularization and fixed point argument. Numerical simulations are performed in order to illustrate the behavior of the model.
We prove the global existence, along with some basic boundedness properties, of weak solutions to a PDE-ODE system modeling the multiscale invasion of tumor cells through the surrounding tissue matrix. The model has been proposed in [22] and accounts on the macroscopic level for the evolution of cell and tissue densities, along with the concentration of a chemoattractant, while on the subcellular level it involves the binding of integrins to soluble and insoluble components of the peritumoral region. The connection between the two scales is realized with the aid of a contractivity function characterizing the ability of the tumor cells to adapt their motility behavior
to their subcellular dynamics.
The resulting system, consisting of three partial and three ordinary differential equations including a temporal delay, in particular involves chemotactic and haptotactic cross-diffusion. In order to overcome technical obstacles stemming from the corresponding highest-order interaction terms, we base our analysis on a certain functional, inter alia involving the cell and tissue densities in the diffusion and haptotaxis terms respectively, which is shown to enjoy a quasi-dissipative property. This will be used as a starting point for the derivation of a series of integral estimates finally allowing for the construction of a generalized solution as the limit of solutions to suitably regularized problems.
Cancer cell migration is an essential feature in the process of tumor spread and establishing of metastasis. It characterizes the invasion observed on the level of the cell population, but it is also tightly connected to the events taking place on the subcellular level. These are conditioning the motile and proliferative behavior of the cells, but are also influenced by it. In this work we propose a multiscale model linking these two levels and aiming to assess their interdependence. On the subcellular, microscopic scale it accounts for integrin binding to soluble and insoluble components present in the peritumoral environment, which is seen as the onset of biochemical events leading to changes in the cell's ability to contract and modify its shape. On the macroscale of the cell population this leads to modifications in the diffusion and haptotaxis performed by the tumor cells and implicitly to changes in the tumor environment. We prove the (local) well posedness of our model and perform numerical simulations in order to illustrate the model predictions.