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A mathematical framework for modelling the metastatic spread of cancer

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A mathematical framework for modelling the metastatic spread of cancer. / Franssen, Linnea Christin; Lorenzi, Tommaso; Burgess, Andrew; Chaplain, Mark Andrew Joseph.

In: Bulletin of Mathematical Biology, Vol. First Online, 22.03.2019.

Research output: Contribution to journalArticle

Harvard

Franssen, LC, Lorenzi, T, Burgess, A & Chaplain, MAJ 2019, 'A mathematical framework for modelling the metastatic spread of cancer', Bulletin of Mathematical Biology, vol. First Online. https://doi.org/10.1007/s11538-019-00597-x

APA

Franssen, L. C., Lorenzi, T., Burgess, A., & Chaplain, M. A. J. (2019). A mathematical framework for modelling the metastatic spread of cancer. Bulletin of Mathematical Biology, First Online. https://doi.org/10.1007/s11538-019-00597-x

Vancouver

Franssen LC, Lorenzi T, Burgess A, Chaplain MAJ. A mathematical framework for modelling the metastatic spread of cancer. Bulletin of Mathematical Biology. 2019 Mar 22;First Online. https://doi.org/10.1007/s11538-019-00597-x

Author

Franssen, Linnea Christin ; Lorenzi, Tommaso ; Burgess, Andrew ; Chaplain, Mark Andrew Joseph. / A mathematical framework for modelling the metastatic spread of cancer. In: Bulletin of Mathematical Biology. 2019 ; Vol. First Online.

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@article{711e5b19f9d340a38b9df72bc6fbdc40,
title = "A mathematical framework for modelling the metastatic spread of cancer",
abstract = "Cancer is a complex disease that starts with mutations of key genes in one cell or a small group of cells at a primary site in the body. If these cancer cells continue to grow successfully and, at some later stage, invade the surrounding tissue and acquire a vascular network, they can spread to distant secondary sites in the body. This process, known as metastatic spread, is responsible for around 90{\%} of deaths from cancer and is one of the so-called hallmarks of cancer. To shed light on the metastatic process, we present a mathematical modelling framework that captures for the first time the interconnected processes of invasion and metastatic spread of individual cancer cells in a spatially explicit manner—a multigrid, hybrid, individual-based approach. This framework accounts for the spatiotemporal evolution of mesenchymal- and epithelial-like cancer cells, membrane-type-1 matrix metalloproteinase (MT1-MMP) and the diffusible matrix metalloproteinase-2 (MMP-2), and for their interactions with the extracellular matrix. Using computational simulations, we demonstrate that our model captures all the key steps of the invasion-metastasis cascade, i.e. invasion by both heterogeneous cancer cell clusters and by single mesenchymal-like cancer cells; intravasation of these clusters and single cells both via active mechanisms mediated by matrix-degrading enzymes (MDEs) and via passive shedding; circulation of cancer cell clusters and single cancer cells in the vasculature with the associated risk of cell death and disaggregation of clusters; extravasation of clusters and single cells; and metastatic growth at distant secondary sites in the body. By faithfully reproducing experimental results, our simulations support the evidence-based hypothesis that the membrane-bound MT1-MMP is the main driver of invasive spread rather than diffusible MDEs such as MMP-2.",
keywords = "Metastatic spread, Mathematical oncology, Tumour microenvironment, Individual-based model, Multigrid framework",
author = "Franssen, {Linnea Christin} and Tommaso Lorenzi and Andrew Burgess and Chaplain, {Mark Andrew Joseph}",
year = "2019",
month = "3",
day = "22",
doi = "10.1007/s11538-019-00597-x",
language = "English",
volume = "First Online",
journal = "Bulletin of Mathematical Biology",
issn = "0092-8240",
publisher = "Springer",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - A mathematical framework for modelling the metastatic spread of cancer

AU - Franssen, Linnea Christin

AU - Lorenzi, Tommaso

AU - Burgess, Andrew

AU - Chaplain, Mark Andrew Joseph

PY - 2019/3/22

Y1 - 2019/3/22

N2 - Cancer is a complex disease that starts with mutations of key genes in one cell or a small group of cells at a primary site in the body. If these cancer cells continue to grow successfully and, at some later stage, invade the surrounding tissue and acquire a vascular network, they can spread to distant secondary sites in the body. This process, known as metastatic spread, is responsible for around 90% of deaths from cancer and is one of the so-called hallmarks of cancer. To shed light on the metastatic process, we present a mathematical modelling framework that captures for the first time the interconnected processes of invasion and metastatic spread of individual cancer cells in a spatially explicit manner—a multigrid, hybrid, individual-based approach. This framework accounts for the spatiotemporal evolution of mesenchymal- and epithelial-like cancer cells, membrane-type-1 matrix metalloproteinase (MT1-MMP) and the diffusible matrix metalloproteinase-2 (MMP-2), and for their interactions with the extracellular matrix. Using computational simulations, we demonstrate that our model captures all the key steps of the invasion-metastasis cascade, i.e. invasion by both heterogeneous cancer cell clusters and by single mesenchymal-like cancer cells; intravasation of these clusters and single cells both via active mechanisms mediated by matrix-degrading enzymes (MDEs) and via passive shedding; circulation of cancer cell clusters and single cancer cells in the vasculature with the associated risk of cell death and disaggregation of clusters; extravasation of clusters and single cells; and metastatic growth at distant secondary sites in the body. By faithfully reproducing experimental results, our simulations support the evidence-based hypothesis that the membrane-bound MT1-MMP is the main driver of invasive spread rather than diffusible MDEs such as MMP-2.

AB - Cancer is a complex disease that starts with mutations of key genes in one cell or a small group of cells at a primary site in the body. If these cancer cells continue to grow successfully and, at some later stage, invade the surrounding tissue and acquire a vascular network, they can spread to distant secondary sites in the body. This process, known as metastatic spread, is responsible for around 90% of deaths from cancer and is one of the so-called hallmarks of cancer. To shed light on the metastatic process, we present a mathematical modelling framework that captures for the first time the interconnected processes of invasion and metastatic spread of individual cancer cells in a spatially explicit manner—a multigrid, hybrid, individual-based approach. This framework accounts for the spatiotemporal evolution of mesenchymal- and epithelial-like cancer cells, membrane-type-1 matrix metalloproteinase (MT1-MMP) and the diffusible matrix metalloproteinase-2 (MMP-2), and for their interactions with the extracellular matrix. Using computational simulations, we demonstrate that our model captures all the key steps of the invasion-metastasis cascade, i.e. invasion by both heterogeneous cancer cell clusters and by single mesenchymal-like cancer cells; intravasation of these clusters and single cells both via active mechanisms mediated by matrix-degrading enzymes (MDEs) and via passive shedding; circulation of cancer cell clusters and single cancer cells in the vasculature with the associated risk of cell death and disaggregation of clusters; extravasation of clusters and single cells; and metastatic growth at distant secondary sites in the body. By faithfully reproducing experimental results, our simulations support the evidence-based hypothesis that the membrane-bound MT1-MMP is the main driver of invasive spread rather than diffusible MDEs such as MMP-2.

KW - Metastatic spread

KW - Mathematical oncology

KW - Tumour microenvironment

KW - Individual-based model

KW - Multigrid framework

U2 - 10.1007/s11538-019-00597-x

DO - 10.1007/s11538-019-00597-x

M3 - Article

VL - First Online

JO - Bulletin of Mathematical Biology

JF - Bulletin of Mathematical Biology

SN - 0092-8240

ER -

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