Individual Cell-Based Model for In-Vitro Mesothelial Invasion of Ovarian Cancer

Giverso, Chiara; Scianna, Marco; Preziosi, Luigi; Buono, Nicola Lo; Funaro, Ada

doi:10.1051/mmnp/20105109

Cited by 30 publications

(22 citation statements)

References 40 publications

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“…There is a plethora of mathematical models related to tumor invasion and accounting in a more or less direct way for cell-cell and cell-matrix adhesions. Most of them describe individual cell behavior and are discrete -in their majority lattice based (e.g., [29,59], also see [15] for a comprehensive review) or off-lattice (see e.g., [18,53]). The so-called hybrid models have a semidiscrete character: They specify the evolution of cells in a discrete, individual-based way and couple it to that of some tactic signal (e.g., chemoattractant concentration, density of ECM fibers), the latter being modeled in a continuous way via some reaction-(diffusion) equation, see e.g., [2,36,54].…”

Section: Introductionmentioning

confidence: 99%

On a structured multiscale model for acid-mediated tumor invasion: The effects of adhesion and proliferation

Engwer

Stinner

Surulescu

2017

Math. Models Methods Appl. Sci.

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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.

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Section: Introductionmentioning

confidence: 99%

On a structured multiscale model for acid-mediated tumor invasion: The effects of adhesion and proliferation

Engwer

Stinner

Surulescu

2017

Math. Models Methods Appl. Sci.

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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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“…There is a combination of the strength of adhesion and haptotaxis in which finger like shapes are observed [38]. Change in the adhesion properties of cells and the disruption of the hypotactic movement result in less extensively disperses invasion fronts, as confirmed in vitro studies [39,40]. Cell proliferation, which depends on the availability of nutrient in the tumour microenvironment, is the predominate factor for tumour growth.…”

Section: Introductionmentioning

confidence: 69%

Effects of Matrix Metalloproteinase on Tumour Growth and Morphology via Haptotaxis

Cr¹,

Nn²

2016

J Bioengineer & Biomedical Sci

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A tumour invasion model has been developed to examine the influence of diffusible matrix metalloproteinases (MMPs) and the mediated proteolysis of non-diffusible, membrane type MMPs (MT-MMPs) on tumour growth and morphology via haptotaxis. Our results are the first to explore the influence of localized degradation of extracellular matrix (ECM) by MT-MMPs on the morphology of tumours growing in nutrient-rich and nutrient-poor microenvironments. Two-dimensional numerical simulation, using a level-set-based tumour host interface-capturing method, reveals that haptotaxis due to ECM degradation by MMP causes greater instability than with ECM degradation by MT-MMP in low-nutrient environments, even at low proliferation rates; whereas the resulting morphologies are similar for high apoptosis rates. Our simulation results show that while haptotaxis leads to completely different tumour growth rates and morphologies depending on proliferation and apoptosis rates in low-nutrient environment, there are no significant variations when we compare the haptotaxis due to ECM degradation by MMP and MT-MMP, except for low proliferation rates. Focusing on the differences between MMP and MT-MMP mediated effects; our study has important implications in MMP-target validation and MMP-inhibitor-drug development for anti-cancer clinical trials.

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Individual Cell-Based Model for In-Vitro Mesothelial Invasion of Ovarian Cancer

Cited by 30 publications

References 40 publications

On a structured multiscale model for acid-mediated tumor invasion: The effects of adhesion and proliferation

On a structured multiscale model for acid-mediated tumor invasion: The effects of adhesion and proliferation

A Hybrid Model Describing Different Morphologies of Tumor Invasion Fronts

Effects of Matrix Metalloproteinase on Tumour Growth and Morphology via Haptotaxis

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