Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study

Anti-angiogenesis as a treatment strategy for normalizing the microvascular network of tumors is of great interest among researchers, especially in combination with chemotherapy or radiotherapy. According to the vital role that angiogenesis plays in tumor growth and in exposing the tumor to therapeu...

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Main Authors: Mahya Mohammadi, M. Soltani, Cyrus Aghanajafi, Mohammad Kohandel
Format: Article
Language:English
Published: AIMS Press 2023-01-01
Series:Mathematical Biosciences and Engineering
Subjects:
Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2023252?viewType=HTML
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author Mahya Mohammadi
M. Soltani
Cyrus Aghanajafi
Mohammad Kohandel
author_facet Mahya Mohammadi
M. Soltani
Cyrus Aghanajafi
Mohammad Kohandel
author_sort Mahya Mohammadi
collection DOAJ
description Anti-angiogenesis as a treatment strategy for normalizing the microvascular network of tumors is of great interest among researchers, especially in combination with chemotherapy or radiotherapy. According to the vital role that angiogenesis plays in tumor growth and in exposing the tumor to therapeutic agents, this work develops a mathematical framework to study the influence of angiostatin, a plasminogen fragment that shows the anti-angiogenic function, in the evolutionary behavior of tumor-induced angiogenesis. Angiostatin-induced microvascular network reformation is investigated in a two-dimensional space by considering two parent vessels around a circular tumor by a modified discrete angiogenesis model in different tumor sizes. The effects of imposing modifications on the existing model, i.e., the matrix-degrading enzyme effect, proliferation and death of endothelial cells, matrix density function, and a more realistic chemotactic function, are investigated in this study. Results show a decrease in microvascular density in response to the angiostatin. A functional relationship exists between angiostatin's ability to normalize the capillary network and tumor size or progression stage, such that capillary density decreases by 55%, 41%, 24%, and 13% in tumors with a non-dimensional radius of 0.4, 0.3, 0.2, and 0.1, respectively, after angiostatin administration.
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spelling doaj.art-506fa383c629482482bd217eb3a94c7e2023-02-14T01:22:54ZengAIMS PressMathematical Biosciences and Engineering1551-00182023-01-012035448548010.3934/mbe.2023252Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical studyMahya Mohammadi 0M. Soltani1Cyrus Aghanajafi2Mohammad Kohandel31. Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran 19919-43344, Iran 2. Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, Canada1. Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran 19919-43344, Iran3. Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada 4. School of Optometry and Vision Science, Faculty of Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada 5. Advanced Bioengineering Initiative Center, Multidisciplinary International Complex, K. N. Toosi University of Technology, Tehran 19697-64499, Iran 6. Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON N2L 3G1, Canada1. Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran 19919-43344, Iran2. Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, CanadaAnti-angiogenesis as a treatment strategy for normalizing the microvascular network of tumors is of great interest among researchers, especially in combination with chemotherapy or radiotherapy. According to the vital role that angiogenesis plays in tumor growth and in exposing the tumor to therapeutic agents, this work develops a mathematical framework to study the influence of angiostatin, a plasminogen fragment that shows the anti-angiogenic function, in the evolutionary behavior of tumor-induced angiogenesis. Angiostatin-induced microvascular network reformation is investigated in a two-dimensional space by considering two parent vessels around a circular tumor by a modified discrete angiogenesis model in different tumor sizes. The effects of imposing modifications on the existing model, i.e., the matrix-degrading enzyme effect, proliferation and death of endothelial cells, matrix density function, and a more realistic chemotactic function, are investigated in this study. Results show a decrease in microvascular density in response to the angiostatin. A functional relationship exists between angiostatin's ability to normalize the capillary network and tumor size or progression stage, such that capillary density decreases by 55%, 41%, 24%, and 13% in tumors with a non-dimensional radius of 0.4, 0.3, 0.2, and 0.1, respectively, after angiostatin administration.https://www.aimspress.com/article/doi/10.3934/mbe.2023252?viewType=HTMLanti-angiogenesismicrovascular networkangiostatinmodified angiogenesis modelmicrovascular density
spellingShingle Mahya Mohammadi
M. Soltani
Cyrus Aghanajafi
Mohammad Kohandel
Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study
Mathematical Biosciences and Engineering
anti-angiogenesis
microvascular network
angiostatin
modified angiogenesis model
microvascular density
title Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study
title_full Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study
title_fullStr Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study
title_full_unstemmed Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study
title_short Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study
title_sort investigation of the evolution of tumor induced microvascular network under the inhibitory effect of anti angiogenic factor angiostatin a mathematical study
topic anti-angiogenesis
microvascular network
angiostatin
modified angiogenesis model
microvascular density
url https://www.aimspress.com/article/doi/10.3934/mbe.2023252?viewType=HTML
work_keys_str_mv AT mahyamohammadi investigationoftheevolutionoftumorinducedmicrovascularnetworkundertheinhibitoryeffectofantiangiogenicfactorangiostatinamathematicalstudy
AT msoltani investigationoftheevolutionoftumorinducedmicrovascularnetworkundertheinhibitoryeffectofantiangiogenicfactorangiostatinamathematicalstudy
AT cyrusaghanajafi investigationoftheevolutionoftumorinducedmicrovascularnetworkundertheinhibitoryeffectofantiangiogenicfactorangiostatinamathematicalstudy
AT mohammadkohandel investigationoftheevolutionoftumorinducedmicrovascularnetworkundertheinhibitoryeffectofantiangiogenicfactorangiostatinamathematicalstudy