Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

Abstract Colorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic...

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Autores principales:	Yafei Wang, Erik Brodin, Kenichiro Nishii, Hermann B. Frieboes, Shannon M. Mumenthaler, Jessica L. Sparks, Paul Macklin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f03941826794ab58b258f2ed63f2cdd
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spelling	oai:doaj.org-article:7f03941826794ab58b258f2ed63f2cdd2021-12-02T13:50:49ZImpact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach10.1038/s41598-020-78780-72045-2322https://doaj.org/article/7f03941826794ab58b258f2ed63f2cdd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78780-7https://doaj.org/toc/2045-2322Abstract Colorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could “reawaken” after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.Yafei WangErik BrodinKenichiro NishiiHermann B. FrieboesShannon M. MumenthalerJessica L. SparksPaul MacklinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yafei Wang Erik Brodin Kenichiro Nishii Hermann B. Frieboes Shannon M. Mumenthaler Jessica L. Sparks Paul Macklin Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
description	Abstract Colorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could “reawaken” after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.
format	article
author	Yafei Wang Erik Brodin Kenichiro Nishii Hermann B. Frieboes Shannon M. Mumenthaler Jessica L. Sparks Paul Macklin
author_facet	Yafei Wang Erik Brodin Kenichiro Nishii Hermann B. Frieboes Shannon M. Mumenthaler Jessica L. Sparks Paul Macklin
author_sort	Yafei Wang
title	Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
title_short	Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
title_full	Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
title_fullStr	Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
title_full_unstemmed	Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
title_sort	impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7f03941826794ab58b258f2ed63f2cdd
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Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

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