Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies
- Autores
- Luján, Emmanuel; Soto, Daniela; Rosito, María Sol; Soba, Alejandro; Guerra, Liliana Noemi; Calvo, Juan Carlos; Marshall, Guillermo Ricardo; Suárez, Cecilia Ana
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Luján, Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Simulación Computacional para Aplicaciones Tecnológicas; Argentina
Fil: Soto, Daniela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Rosito, María Sol. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentina
Fil: Soba, Alejandro. Comisión Nacional de Energía Atómica; Argentina
Fil: Guerra, Liliana Noemi. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Calvo, Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Marshall, Guillermo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
Fil: Suárez, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina - Materia
-
Microtumoural Infiltration
Multicellular Spheroids
In Silico Models
Fractals - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/80640
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Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studiesLuján, EmmanuelSoto, DanielaRosito, María SolSoba, AlejandroGuerra, Liliana NoemiCalvo, Juan CarlosMarshall, Guillermo RicardoSuárez, Cecilia AnaMicrotumoural InfiltrationMulticellular SpheroidsIn Silico ModelsFractalsMathematical 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.Fil: Luján, Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Simulación Computacional para Aplicaciones Tecnológicas; ArgentinaFil: Soto, Daniela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Rosito, María Sol. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Soba, Alejandro. Comisión Nacional de Energía Atómica; ArgentinaFil: Guerra, Liliana Noemi. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Calvo, Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Marshall, Guillermo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Suárez, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaRoyal Society of Chemistry2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/80640Luján, Emmanuel; Soto, Daniela; Rosito, María Sol; Soba, Alejandro; Guerra, Liliana Noemi; et al.; Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies; Royal Society of Chemistry; Integrative Biology; 10; 5; 5-2018; 325-3341757-9694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1039/c8ib00049binfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:37:22Zoai:ri.conicet.gov.ar:11336/80640instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:37:22.328CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
title |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
spellingShingle |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies Luján, Emmanuel Microtumoural Infiltration Multicellular Spheroids In Silico Models Fractals |
title_short |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
title_full |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
title_fullStr |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
title_full_unstemmed |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
title_sort |
Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies |
dc.creator.none.fl_str_mv |
Luján, Emmanuel Soto, Daniela Rosito, María Sol Soba, Alejandro Guerra, Liliana Noemi Calvo, Juan Carlos Marshall, Guillermo Ricardo Suárez, Cecilia Ana |
author |
Luján, Emmanuel |
author_facet |
Luján, Emmanuel Soto, Daniela Rosito, María Sol Soba, Alejandro Guerra, Liliana Noemi Calvo, Juan Carlos Marshall, Guillermo Ricardo Suárez, Cecilia Ana |
author_role |
author |
author2 |
Soto, Daniela Rosito, María Sol Soba, Alejandro Guerra, Liliana Noemi Calvo, Juan Carlos Marshall, Guillermo Ricardo Suárez, Cecilia Ana |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Microtumoural Infiltration Multicellular Spheroids In Silico Models Fractals |
topic |
Microtumoural Infiltration Multicellular Spheroids In Silico Models Fractals |
dc.description.none.fl_txt_mv |
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. Fil: Luján, Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Simulación Computacional para Aplicaciones Tecnológicas; Argentina Fil: Soto, Daniela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Rosito, María Sol. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentina Fil: Soba, Alejandro. Comisión Nacional de Energía Atómica; Argentina Fil: Guerra, Liliana Noemi. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Calvo, Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Marshall, Guillermo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina Fil: Suárez, Cecilia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina |
description |
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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-05 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/80640 Luján, Emmanuel; Soto, Daniela; Rosito, María Sol; Soba, Alejandro; Guerra, Liliana Noemi; et al.; Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies; Royal Society of Chemistry; Integrative Biology; 10; 5; 5-2018; 325-334 1757-9694 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/80640 |
identifier_str_mv |
Luján, Emmanuel; Soto, Daniela; Rosito, María Sol; Soba, Alejandro; Guerra, Liliana Noemi; et al.; Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by: In vitro studies; Royal Society of Chemistry; Integrative Biology; 10; 5; 5-2018; 325-334 1757-9694 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1039/c8ib00049b |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Royal Society of Chemistry |
publisher.none.fl_str_mv |
Royal Society of Chemistry |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614393889816576 |
score |
13.070432 |