Intracellular Modelling of Cell-Matrix Adhesion during Cancer Cell Invasion

Andasari, Vivi; Chaplain, M. A. J.

doi:10.1051/mmnp/20127103

Cited by 18 publications

(13 citation statements)

References 56 publications

(49 reference statements)

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“…Such a comparison is given by Andasari and colleagues, who studied how cell-cell adhesion and metastasis is influenced by cell signaling in epithelial tumors. They directly compared their results obtained using a CPM (Andasari and Chaplain, 2012) with results from a cell-center model (Andasari et al, 2011). While in the cell-center model the malignant cells leave the epithelium in a wave, spreading radially outwards from an initial cell, in the CPM this radial pattern becomes more stochastic and irregular.…”

Section: Discussionmentioning

confidence: 99%

Cellular Potts Modeling of Tumor Growth, Tumor Invasion, and Tumor Evolution

Szabó¹,

Merks²

2013

Front. Oncol.

167

130

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Despite a growing wealth of available molecular data, the growth of tumors, invasion of tumors into healthy tissue, and response of tumors to therapies are still poorly understood. Although genetic mutations are in general the first step in the development of a cancer, for the mutated cell to persist in a tissue, it must compete against the other, healthy or diseased cells, for example by becoming more motile, adhesive, or multiplying faster. Thus, the cellular phenotype determines the success of a cancer cell in competition with its neighbors, irrespective of the genetic mutations or physiological alterations that gave rise to the altered phenotype. What phenotypes can make a cell “successful” in an environment of healthy and cancerous cells, and how? A widely used tool for getting more insight into that question is cell-based modeling. Cell-based models constitute a class of computational, agent-based models that mimic biophysical and molecular interactions between cells. One of the most widely used cell-based modeling formalisms is the cellular Potts model (CPM), a lattice-based, multi particle cell-based modeling approach. The CPM has become a popular and accessible method for modeling mechanisms of multicellular processes including cell sorting, gastrulation, or angiogenesis. The CPM accounts for biophysical cellular properties, including cell proliferation, cell motility, and cell adhesion, which play a key role in cancer. Multiscale models are constructed by extending the agents with intracellular processes including metabolism, growth, and signaling. Here we review the use of the CPM for modeling tumor growth, tumor invasion, and tumor progression. We argue that the accessibility and flexibility of the CPM, and its accurate, yet coarse-grained and computationally efficient representation of cell and tissue biophysics, make the CPM the method of choice for modeling cellular processes in tumor development.

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Section: Discussionmentioning

confidence: 99%

Cellular Potts Modeling of Tumor Growth, Tumor Invasion, and Tumor Evolution

Szabó¹,

Merks²

2013

Front. Oncol.

167

130

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“…Existing mathematical models that analyse effects of cell adhesion on tumour cell dissemination differ by the specific choice of mechanisms included in their respective definitions [ 26 – 30 ] (see also [ 31 ] for an overview of models for analysing effects of cell adhesion on cell dissemination). Aspects of adhesion heterogeneity are not considered in any of these models.…”

Section: Introductionmentioning

confidence: 99%

Cell adhesion heterogeneity reinforces tumour cell dissemination: novel insights from a mathematical model

et al. 2017

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BackgroundCancer cell invasion, dissemination, and metastasis have been linked to an epithelial-mesenchymal transition (EMT) of individual tumour cells. During EMT, adhesion molecules like E-cadherin are downregulated and the decrease of cell-cell adhesion allows tumour cells to dissociate from the primary tumour mass. This complex process depends on intracellular cues that are subject to genetic and epigenetic variability, as well as extrinsic cues from the local environment resulting in a spatial heterogeneity in the adhesive phenotype of individual tumour cells. Here, we use a novel mathematical model to study how adhesion heterogeneity, influenced by intrinsic and extrinsic factors, affects the dissemination of tumour cells from an epithelial cell population. The model is a multiscale cellular automaton that couples intracellular adhesion receptor regulation with cell-cell adhesion.ResultsSimulations of our mathematical model indicate profound effects of adhesion heterogeneity on tumour cell dissemination. In particular, we show that a large variation of intracellular adhesion receptor concentrations in a cell population reinforces cell dissemination, regardless of extrinsic cues mediated through the local cell density. However, additional control of adhesion receptor concentration through the local cell density, which can be assumed in healthy cells, weakens the effect. Furthermore, we provide evidence that adhesion heterogeneity can explain the remarkable differences in adhesion receptor concentrations of epithelial and mesenchymal phenotypes observed during EMT and might drive early dissemination of tumour cells.ConclusionsOur results suggest that adhesion heterogeneity may be a universal trigger to reinforce cell dissemination in epithelial cell populations. This effect can be at least partially compensated by a control of adhesion receptor regulation through neighbouring cells. Accordingly, our findings explain how both an increase in intra-tumour adhesion heterogeneity and the loss of control through the local environment can promote tumour cell dissemination.ReviewersThis article was reviewed by Hanspeter Herzel, Thomas Dandekar and Marek Kimmel.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-017-0188-z) contains supplementary material, which is available to authorized users.

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“…Recently, these modelling efforts have been expanded to try to develop models which reflect the multiscale character of cancer invasion (Deisboeck et al, 2011;Macklin et al, 2009;Ramis-Conde et al, 2008;Trucu et al, 2013). The central role of cell-cell and cell-matrix adhesion in tumour cell invasion has received a special attention (Andasari and Chaplain, 2012;Anderson, 2005;Byrne and Chaplain, 1996;Chaplain et al, 2011;Painter et al, 2010;Ramis-Conde et al, 2008;Turner and Sherratt, 2002), remaining one of the core challenges in mathematical modelling.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of cancer invasion: Implications of cell adhesion variability for tumour infiltrative growth patterns

Domschke

Trucu

Gerisch

et al. 2014

Journal of Theoretical Biology

131

144

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Cancer invasion, recognised as one of the hallmarks of cancer, is a complex, multiscale phenomenon involving many inter-related genetic, biochemical, cellular and tissue processes at different spatial and temporal scales. Central to invasion is the ability of cancer cells to alter and degrade an extracellular matrix. Combined with abnormal excessive proliferation and migration which is enabled and enhanced by altered cell-cell and cell-matrix adhesion, the cancerous mass can invade the neighbouring tissue. Along with tumour-induced angiogenesis, invasion is a key component of metastatic spread, ultimately leading to the formation of secondary tumours in other parts of the host body. In this paper we explore the spatio-temporal dynamics of a model of cancer invasion, where cell-cell and cell-matrix adhesion is accounted for through non-local interaction terms in a system of partial integro-differential equations. The change of adhesion properties during cancer growth and development is investigated here through time-dependent adhesion characteristics within the cell population as well as those between the cells and the components of the extracellular matrix. Our computational simulation results demonstrate a range of heterogeneous dynamics which are qualitatively similar to the invasive growth patterns observed in a number of different types of cancer, such as tumour infiltrative growth patterns (INF).

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Intracellular Modelling of Cell-Matrix Adhesion during Cancer Cell Invasion

Cited by 18 publications

References 56 publications

Cellular Potts Modeling of Tumor Growth, Tumor Invasion, and Tumor Evolution

Cellular Potts Modeling of Tumor Growth, Tumor Invasion, and Tumor Evolution

Cell adhesion heterogeneity reinforces tumour cell dissemination: novel insights from a mathematical model

Mathematical modelling of cancer invasion: Implications of cell adhesion variability for tumour infiltrative growth patterns

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