Modeling the Influence of the E-Cadherin-β-Catenin Pathway in Cancer Cell Invasion: A Multiscale Approach

Ramis-Conde, Ignacio; Drasdo, Dirk; Anderson, Alexander R.A.; Chaplain, M. A. J.

doi:10.1529/biophysj.107.114678

Cited by 220 publications

(224 citation statements)

References 35 publications

(43 reference statements)

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“…Direct representations of adhesion were first considered in the context of individual cell-based models (Turner & Sherratt 2002;Turner et al 2004;Grygierzec et al 2004). In recent years, this modelling approach has been developed significantly by Anderson and coworkers, in a series of sophisticated studies into the ways in which changes in cell-cell and cell-5 A c c e p t e d m a n u s c r i p t matrix adhesion interact with other aspects of the invasive phenotype (Anderson et al 2006Ramis-Conde et al 2008;Poplawski et al 2009). …”

Section: Modelling Adhesion In Invasion Processesmentioning

confidence: 99%

The impact of adhesion on cellular invasion processes in cancer and development

Painter

Armstrong

Sherratt

2010

Journal of Theoretical Biology

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In this paper we consider a simple continuous model to describe cell invasion, incorporating the effects of both cell-cell adhesion and cell-matrix adhesion, along with cell growth and proteolysis by cells of the surrounding extracellular matrix (ECM).We demonstrate that the model is capable of supporting both noninvasive and invasive tumour growth according to the relative strength of cell-cell to cell-matrix adhesion. Specifically, for sufficiently strong cell-matrix adhesion and/or sufficiently weak cell-cell adhesion, degradation of the surrounding ECM accompanied by cellmatrix adhesion pulls the cells into the surrounding ECM. We investigate the criticality of matrix heterogeneity on shaping invasion, demonstrating that a highly heterogeneous ECM can result in a "fingering" of the invasive front, echoing observations in real-life invasion processes ranging from malignant tumour growth to neural crest migration during embryonic development.

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Section: Modelling Adhesion In Invasion Processesmentioning

confidence: 99%

The impact of adhesion on cellular invasion processes in cancer and development

Painter

Armstrong

Sherratt

2010

Journal of Theoretical Biology

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“…In particular, the production of proteolytic enzymes, such as matrix metalloproteinases (MMPs), is essential during the invasive phase: the dissolution of the ECM provides in fact both a space into which aggressive cells can move and a gradient which can be used by the cells themselves to direct their movement (i.e., haptotaxis), see [14,48,68]. The scattered individuals, evading destruction by the immune system, may subsequently enter the host bloodstream or lymphatics, extravasate at a distant site, and establish secondary colonies with devastating consequences for the wellbeing of the patient, as the likelihood of success of therapeutic interventions strongly decreases, as modeled in [25,55].…”

Section: Introductionmentioning

confidence: 99%

A Hybrid Model Describing Different Morphologies of Tumor Invasion Fronts

Scianna

Preziosi

2012

Math. Model. Nat. Phenom.

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Abstract. The invasive capability is fundamental in determining the malignancy of a solid tumor. Revealing biomedical strategies that are able to partially decrease cancer invasiveness is therefore an important approach in the treatment of the disease and has given rise to multiple in vitro and in silico models. We here develop a hybrid computational framework, whose aim is to characterize the effects of the different cellular and subcellular mechanisms involved in the invasion of a malignant mass. In particular, a discrete Cellular Potts Model is used to represent the population of cancer cells at the mesoscopic scale, while a continuous approach of reaction-diffusion equations is employed to describe the evolution of microscopic variables, as the nutrients and the proteins present in the microenvironment and the matrix degrading enzymes secreted by the tumor. The behavior of each cell is then determined by a balance of forces, such as homotypic (cell-cell) and heterotypic (cell-matrix) adhesions and haptotaxis, and is mediated by the internal state of the individual, i.e. its motility. The resulting composite model quantifies the influence of changes in the mechanisms involved in tumor invasion and, more interestingly, puts in evidence possible therapeutic approaches, that are potentially effective in decreasing the malignancy of the disease, such as the alteration in the adhesive properties of the cells, the inhibition in their ability to remodel and the disruption of the haptotactic movement. We also extend the simulation framework by including cell proliferation which, following experimental evidence, is regulated by the intracellular level of growth factors. Interestingly, in spite of the increment in cellular density, the depth of invasion is not significantly increased, as one could have expected.

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“…This means that the formation of adhesive bonds can alter the intracellular structure and directly affect cell mobility. In the context of cancer invasion, this was already acknowledged in theoretical models [Gerisch and Chaplain, 2008;Ramis-Conde, Drasdo, Anderson and Chaplain, 2008]. Thus the analogy between liquids and tissues cannot be simply transferred to cell level.…”

Section: Introductionmentioning

confidence: 99%

The cellular basis of cell sorting kinetics

Voß-Böhme

Deutsch

2010

Journal of Theoretical Biology

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Cell sorting is a dynamical cooperative phenomenon that is fundamental for tissue morphogenesis and tissue homeostasis. According to Steinberg's differential adhesion hypothesis, the structure of sorted cell aggregates is determined by physical characteristics of the respective tissues, the tissue surface tensions. Steinberg postulated that tissue surface tensions result from quantitative differences in intercellular adhesion. Several experiments in cell cultures as well as in developing organisms support this hypothesis.The question of how tissue surface tension might result from differential adhesion was addressed in some theoretical models. These models describe the cellular interdependence structure once the temporal evolution has stabilized. In general, these models are capable of reproducing sorted patterns. However the model dynamics at the cellular scale are defined implicitly and are not welljustified. The precise mechanism describing how differential adhesion generates the observed sorting kinetics at the tissue level is still unclear.It is necessary to formulate the concepts of cell level kinetics explicitly. Only then it is possible to understand the temporal development at the cellular and tissue scales. Here we argue that individual cell mobility is reduced the more the cells stick to their neighbors. We translate this assumption into a precise mathematical model which belongs to the class of stochastic interacting particle systems. Analyzing this model, we are able to predict the emergent sorting behavior at the population level. We describe qualitatively the geometry of cell segregation depending on the intercellular adhesion parameters. Furthermore, we derive a functional relationship between intercellular adhesion and surface tension and highlight the role of cell mobility in the process of sorting. We show that the interaction between the cells and the boundary of a confining vessel has a major impact on the sorting geometry.Keywords: differential adhesion hypothesis, tissue surface tension, phase segregation, stochastic lattice gas, interacting particle system 2000 MSC: 92C15, 92C17, 92C37 * Corresponding author Email addresses: anja.voss-boehme@tu-dresden.de (A. Voß-Böhme), andreas.deutsch@tu-dresden.de (A. Deutsch) Preprint submitted to Elsevier 4th December 2009A c c e p t e d m a n u s c r i p t

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Modeling the Influence of the E-Cadherin-β-Catenin Pathway in Cancer Cell Invasion: A Multiscale Approach

Cited by 220 publications

References 35 publications

The impact of adhesion on cellular invasion processes in cancer and development

The impact of adhesion on cellular invasion processes in cancer and development

A Hybrid Model Describing Different Morphologies of Tumor Invasion Fronts

The cellular basis of cell sorting kinetics

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