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A Hybrid Model Describing Different Morphologies of TumorInvasion Fronts

Published online by Cambridge University Press:  25 January 2012

M. Scianna  and
L. Preziosi
M. Scianna
Affiliation:
Department of Mathematics, Politecnico di Torino Corso Duca degli Abruzzi 24, 10129 Torino, Italy Institute for Cancer Research and Treatment Strada Provinciale 142, 10060 Candiolo, Italy
L. Preziosi*
Affiliation:
Department of Mathematics, Politecnico di Torino Corso Duca degli Abruzzi 24, 10129 Torino, Italy
*
⋆ Corresponding author. E-mail: luigi.preziosi@polito.it
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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 istherefore an important approach in the treatment of the disease and has given rise tomultiple in vitro and in silico models. We here developa hybrid computational framework, whose aim is to characterize the effects of thedifferent cellular and subcellular mechanisms involved in the invasion of a malignantmass. In particular, a discrete Cellular Potts Model is used to represent the populationof cancer cells at the mesoscopic scale, while a continuous approach of reaction-diffusionequations is employed to describe the evolution of microscopic variables, as the nutrientsand the proteins present in the microenvironment and the matrix degrading enzymes secretedby the tumor. The behavior of each cell is then determined by a balance of forces, such ashomotypic (cell-cell) and heterotypic (cell-matrix) adhesions and haptotaxis, and ismediated by the internal state of the individual, i.e. its motility. The resultingcomposite model quantifies the influence of changes in the mechanisms involved in tumorinvasion and, more interestingly, puts in evidence possible therapeutic approaches, thatare potentially effective in decreasing the malignancy of the disease, such as thealteration in the adhesive properties of the cells, the inhibition in their ability toremodel and the disruption of the haptotactic movement. We also extend the simulationframework by including cell proliferation which, following experimental evidence, isregulated by the intracellular level of growth factors. Interestingly, in spite of theincrement in cellular density, the depth of invasion is not significantly increased, asone could have expected.

Keywords

cellular potts modeltumor invasion matrixmetalloproteinases
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 7 , Issue 1: Cancer modeling , 2012 , pp. 78 - 104
Copyright
© EDP Sciences, 2012

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