The present mathematical models of microtumours consider, in general, volumetric growth and spherical tumour invasion shapes. Nevertheless in many cases, such as in gliomas, a need for more accurate delineation of tumour infiltration areas in a patient-specific manner has arisen. The objective of this study was to build a mathematical model able to describe in a case-specific way as well as to predict in a probabilistic way the growth and the real invasion pattern of multicellular tumour spheroids (in vitro model of an avascular microtumour) immersed in a collagen matrix. The two-dimensional theoretical model was represented by a reaction-convection-diffusion equation that considers logistic proliferation, volumetric growth, a rim with proliferative cells at the tumour surface and invasion with diffusive and convective components. Population parameter values of the model were extracted from the experimental dataset and a shape function that describes the invasion area was derived from each experimental case by image processing. New possible and aleatory shape functions were generated by data mining and Monte Carlo tools by means of a satellite EGARCH model, which were fed with all the shape functions of the dataset. Then the main model is used in two different ways: to reproduce the growth and invasion of a given experimental tumour in a case-specific manner when fed with the corresponding shape function (descriptive simulations) or to generate new possible tumour cases that respond to the general population pattern when fed with an aleatory-generated shape function (predictive simulations). Both types of simulations are in good agreement with empirical data, as it was revealed by area quantification and Bland-Altman analysis. This kind of experimental-numerical interaction has wide application potential in designing new strategies able to predict as much as possible the invasive behaviour of a tumour based on its particular characteristics and microenvironment. © 2016 The Royal Society of Chemistry.
Documento: | Artículo |
Título: | Mathematical modelling of microtumour infiltration based on in vitro experiments |
Autor: | Luján, E.; Guerra, L.N.; Soba, A.; Visacovsky, N.; Gandía, D.; Calvo, J.C.; Suárez, C. |
Filiación: | Laboratorio de Sistemas Complejos, Departamento de Computación, Instituto de Física Del Plasma, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina Centro de Simulación Computacional Para Aplicaciones Tecnológicas, CONICET, Buenos Aires, Argentina Sanatorio Los Arcos, Buenos Aires, Argentina |
Palabras clave: | animal cell; animal experiment; Article; cell proliferation; collagen degradation; controlled study; diffusion coefficient; epithelium cell; experimental neoplasm; image processing; in vitro study; mathematical model; Monte Carlo method; mouse; nonhuman; phenotype; priority journal; surface property; tumor cell; tumor invasion; tumor microenvironment; tumor spheroid; animal; biological model; biophysics; brain tumor; computer simulation; epithelium; glioma; human; metabolism; microcirculation; multicellular spheroid; neoplasm; pathology; Animals; Biophysical Phenomena; Brain Neoplasms; Cell Proliferation; Computer Simulation; Epithelium; Glioma; Humans; Image Processing, Computer-Assisted; In Vitro Techniques; Mice; Microcirculation; Models, Biological; Monte Carlo Method; Neoplasm Invasiveness; Neoplasms; Spheroids, Cellular |
Año: | 2016 |
Volumen: | 8 |
Número: | 8 |
Página de inicio: | 879 |
Página de fin: | 885 |
DOI: | http://dx.doi.org/10.1039/c6ib00110f |
Título revista: | Integrative Biology (United Kingdom) |
Título revista abreviado: | Integr. Biol. |
ISSN: | 17579694 |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17579694_v8_n8_p879_Lujan |