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Coupling of discrete random walks and continuous modeling for three-dimensional tumor-induced angiogenesis

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Abstract

The growth of new vascular networks from pre-existing capillaries (angiogenesis) plays a pivotal role in tumor development. Mathematical modeling of tumor-induced angiogenesis may help understand the underlying biology of the process and provide new hypotheses for experimentation. Here, we couple an existing deterministic continuum theory with a discrete random walk, proposing a new model that accounts for chemotactic and haptotactic cellular migration. We propose an efficient numerical method to approximate the solution of the model. The accuracy, stability and effectiveness of our algorithms permitted us to perform large-scale three-dimensional simulations which, in contrast to two-dimensional calculations, show a topological complexity similar to that found in experiments. Finally, we use our model and simulations to investigate the role of haptotaxis and chemotaxis in the mobility of tip endothelial cells and its influence in the final vascular patterns.

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Acknowledgments

HG was partially supported by the European Research Council through the FP7 Ideas Starting Grant program (Project #307201) and by Consellería de Educación e Ordenación Universitaria de la Xunta de Galicia. IC was partially supported by Consellería de Educación e Ordenación Universitaria de la Xunta de Galicia (Grant #CN2011/002). This support is gratefully acknowledged.

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Correspondence to Guillermo Vilanova.

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Vilanova, G., Colominas, I. & Gomez, H. Coupling of discrete random walks and continuous modeling for three-dimensional tumor-induced angiogenesis. Comput Mech 53, 449–464 (2014). https://doi.org/10.1007/s00466-013-0958-0

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