Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression

Abstract Excessive tumour growth results in a hypoxic environment around cancer cells, thus inducing tumour angiogenesis, which refers to the generation of new blood vessels from pre-existing vessels. This mechanism is biologically and physically complex, with various mathematical simulation models...

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Autores principales:	Hayato Yanagisawa, Masahiro Sugimoto, Tomoyuki Miyashita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09d523bee4684cfe980bd21d34964a57
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spelling	oai:doaj.org-article:09d523bee4684cfe980bd21d34964a572021-12-02T14:12:42ZMathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression10.1038/s41598-020-79824-82045-2322https://doaj.org/article/09d523bee4684cfe980bd21d34964a572021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79824-8https://doaj.org/toc/2045-2322Abstract Excessive tumour growth results in a hypoxic environment around cancer cells, thus inducing tumour angiogenesis, which refers to the generation of new blood vessels from pre-existing vessels. This mechanism is biologically and physically complex, with various mathematical simulation models proposing to reproduce its formation. However, although temporary vessel regression is clinically known, few models succeed in reproducing this phenomenon. Here, we developed a three-dimensional simulation model encompassing both angiogenesis and tumour growth, specifically including angiopoietin. Angiopoietin regulates both adhesion and migration between vascular endothelial cells and wall cells, thus inhibiting the cell-to-cell adhesion required for angiogenesis initiation. Simulation results showed a regression, i.e. transient decrease, in the overall length of new vessels during vascular network formation. Using our model, we also evaluated the efficacy of administering the drug bevacizumab. The results highlighted differences in treatment efficacy: (1) earlier administration showed higher efficacy in inhibiting tumour growth, and (2) efficacy depended on the treatment interval even with the administration of the same dose. After thorough validation in the future, these results will contribute to the design of angiogenesis treatment protocols.Hayato YanagisawaMasahiro SugimotoTomoyuki MiyashitaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hayato Yanagisawa Masahiro Sugimoto Tomoyuki Miyashita Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
description	Abstract Excessive tumour growth results in a hypoxic environment around cancer cells, thus inducing tumour angiogenesis, which refers to the generation of new blood vessels from pre-existing vessels. This mechanism is biologically and physically complex, with various mathematical simulation models proposing to reproduce its formation. However, although temporary vessel regression is clinically known, few models succeed in reproducing this phenomenon. Here, we developed a three-dimensional simulation model encompassing both angiogenesis and tumour growth, specifically including angiopoietin. Angiopoietin regulates both adhesion and migration between vascular endothelial cells and wall cells, thus inhibiting the cell-to-cell adhesion required for angiogenesis initiation. Simulation results showed a regression, i.e. transient decrease, in the overall length of new vessels during vascular network formation. Using our model, we also evaluated the efficacy of administering the drug bevacizumab. The results highlighted differences in treatment efficacy: (1) earlier administration showed higher efficacy in inhibiting tumour growth, and (2) efficacy depended on the treatment interval even with the administration of the same dose. After thorough validation in the future, these results will contribute to the design of angiogenesis treatment protocols.
format	article
author	Hayato Yanagisawa Masahiro Sugimoto Tomoyuki Miyashita
author_facet	Hayato Yanagisawa Masahiro Sugimoto Tomoyuki Miyashita
author_sort	Hayato Yanagisawa
title	Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
title_short	Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
title_full	Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
title_fullStr	Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
title_full_unstemmed	Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
title_sort	mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/09d523bee4684cfe980bd21d34964a57
work_keys_str_mv	AT hayatoyanagisawa mathematicalsimulationoftumourangiogenesisangiopoietinbalanceisakeyfactorinvesselgrowthandregression AT masahirosugimoto mathematicalsimulationoftumourangiogenesisangiopoietinbalanceisakeyfactorinvesselgrowthandregression AT tomoyukimiyashita mathematicalsimulationoftumourangiogenesisangiopoietinbalanceisakeyfactorinvesselgrowthandregression
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Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression

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