Abstract:
Mathematical modelling approaches have become increasingly abundant in cancer research. Tumour infiltration extent and its spatial organization depend both on the tumour type and stage and on the bio-physicochemical characteristics of the microenvironment. This sets a complex scenario that often requires a multidisciplinary and individually adjusted approach. The ultimate goal of this work is to present an experimental/numerical combined method for the development of a three-dimensional mathematical model with the ability to reproduce the growth and infiltration patterns of a given avascular microtumour in response to different microenvironmental conditions. The model is based on a diffusion-convection reaction equation that considers logistic proliferation, volumetric growth, a rim of proliferative cells at the tumour surface, and invasion with diffusive and convective components. The parameter values of the model were fitted to experimental results while radial velocity and diffusion coefficients were made spatially variable in a case-specific way through the introduction of a shape function and a diffusion-limited-aggregation (DLA)-derived fractal matrix, respectively, according to the infiltration pattern observed. The in vitro model consists of multicellular tumour spheroids (MTSs) of an epithelial mammary tumour cell line (LM3) immersed in a collagen I gel matrix with a standard culture medium ("naive" matrix) or a conditioned medium from adipocytes or preadipocytes ("conditioned" matrix). It was experimentally determined that both adipocyte and preadipocyte conditioned media had the ability to change the MTS infiltration pattern from collective and laminar to an individual and atomized one. Numerical simulations were able to adequately reproduce qualitatively and quantitatively both kinds of infiltration patterns, which were determined by area quantification, analysis of fractal dimensions and lacunarity, and Bland-Altman analysis. These results suggest that the combined approach presented here could be established as a new framework with interesting potential applications at both the basic and clinical levels in the oncology area. © 2018 The Royal Society of Chemistry.
Registro:
Documento: |
Artículo
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Título: | Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
Autor: | Luján, E.; Soto, D.; Rosito, M.S.; Soba, A.; Guerra, L.N.; Calvo, J.C.; Marshall, G.; Suárez, C. |
Filiación: | Laboratorio de Sistemas Complejos, Instituto de Física Del Plasma, CONICET-UBA, Buenos Aires, Argentina Centro de Simulación Computacional Para Aplicaciones Tecnológicas, CONICET, Buenos Aires, Argentina Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina Instituto de Astronomía y Física Del Espacio, CONICET-UBA, Buenos Aires, Argentina Comisión Nacional de Energía Atómica, CONICET, Buenos Aires, Argentina Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires, Argentina Departamento de Computacion, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina
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Palabras clave: | collagen gel; collagen type 1; adipocyte; animal cell; Article; bland altman analysis; cancer growth; cancer infiltration; cancer research; cell differentiation; cell proliferation; computer model; controlled study; diffusion; diffusion coefficient; fractal analysis; in vitro study; intermethod comparison; LM3 cell line (breast cancer); mathematical analysis; mathematical model; mathematical parameters; mouse; multicellular spheroid; nonhuman; priority journal; proadipocyte; qualitative analysis; quantitative analysis; reproducibility; simulation; thermodynamics; three dimensional imaging; tumor invasion; tumor microenvironment; tumor spheroid; tumor volume; velocity; 3T3-L1 cell line; animal; biological model; conditioned medium; cytology; experimental mammary neoplasm; female; pathology; pathophysiology; physiology; three dimensional imaging; tumor cell line; tumor microenvironment; tumor seeding; 3T3-L1 Cells; Adipocytes; Animals; Cell Line, Tumor; Culture Media, Conditioned; Female; Imaging, Three-Dimensional; Mammary Neoplasms, Experimental; Mice; Models, Biological; Neoplasm Invasiveness; Neoplasm Seeding; Spheroids, Cellular; Tumor Microenvironment |
Año: | 2018
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Volumen: | 10
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Número: | 5
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Página de inicio: | 325
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Página de fin: | 334
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DOI: |
http://dx.doi.org/10.1039/c8ib00049b |
Título revista: | Integrative Biology (United Kingdom)
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Título revista abreviado: | Integr. Biol.
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ISSN: | 17579694
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CAS: | Culture Media, Conditioned
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17579694_v10_n5_p325_Lujan |
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Citas:
---------- APA ----------
Luján, E., Soto, D., Rosito, M.S., Soba, A., Guerra, L.N., Calvo, J.C., Marshall, G.,..., Suárez, C.
(2018)
. Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies. Integrative Biology (United Kingdom), 10(5), 325-334.
http://dx.doi.org/10.1039/c8ib00049b---------- CHICAGO ----------
Luján, E., Soto, D., Rosito, M.S., Soba, A., Guerra, L.N., Calvo, J.C., et al.
"Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies"
. Integrative Biology (United Kingdom) 10, no. 5
(2018) : 325-334.
http://dx.doi.org/10.1039/c8ib00049b---------- MLA ----------
Luján, E., Soto, D., Rosito, M.S., Soba, A., Guerra, L.N., Calvo, J.C., et al.
"Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies"
. Integrative Biology (United Kingdom), vol. 10, no. 5, 2018, pp. 325-334.
http://dx.doi.org/10.1039/c8ib00049b---------- VANCOUVER ----------
Luján, E., Soto, D., Rosito, M.S., Soba, A., Guerra, L.N., Calvo, J.C., et al. Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies. Integr. Biol. 2018;10(5):325-334.
http://dx.doi.org/10.1039/c8ib00049b