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A multiscale in silico model of endothelial to mesenchymal transformation in a tumor microenvironment.

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Title: A multiscale in silico model of endothelial to mesenchymal transformation in a tumor microenvironment.
Authors: Chowkwale, M.1 (AUTHOR), Mahler, G.J.1 (AUTHOR), Huang, P.2 (AUTHOR), Murray, B.T.1,2 (AUTHOR) bmurray@binghamton.edu
Source: Journal of Theoretical Biology. Nov2019, Vol. 480, p229-240. 12p.
Subjects: Multiscale modeling, Tumor microenvironment, Myofibroblasts, Extracellular matrix, Tissue remodeling, Cell migration
Abstract: • An in silico model of endothelial to mesenchymal transformation was created. • The computational model uses a hybrid discrete-continuum approach to mimic an in vitro tumor model. • Demonstrates the effects of EndMT-derived activated fibroblasts on tumor cell migration and proliferation. • Elucidates extracellular matrix stiffness-dependent behavior of tumor cells. • Provides a platform to study interactions of EndMT-derived activated fibroblasts, extracellular matrix, and tumors. Endothelial to mesenchymal transformation (EndMT) is a process in which endothelial cells gain a mesenchymal-like phenotype in response to mechanobiological signals that results in the remodeling or repair of underlying tissue. While initially associated with embryonic development, this process has since been shown to occur in adult tissue remodeling including wound healing, fibrosis, and cancer. In an attempt to understand the role of EndMT in cancer progression and metastasis, we present a multiscale, three-dimensional, in silico model. The model couples tissue level phenomena such as extracellular matrix remodeling, cellular level phenomena such as migration and proliferation, and chemical transport in the tumor microenvironment to mimic in vitro tissue models of the cancer microenvironment. The model is used to study the presence of EndMT-derived activated fibroblasts (EDAFs) and varying substrate stiffness on tumor cell migration and proliferation. The simulations accurately model the behavior of tumor cells under given conditions. The presence of EDAFs and/or an increase in substrate stiffness resulted in an increase in tumor cell activity. This model lays the foundation of further studies of EDAFs in a tumor microenvironment on a cellular and subcellular physiological level. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Theoretical Biology is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
An: 138438108
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
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  Data: A multiscale in silico model of endothelial to mesenchymal transformation in a tumor microenvironment.
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  Data: <searchLink fieldCode="AR" term="%22Chowkwale%2C+M%2E%22">Chowkwale, M.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mahler%2C+G%2EJ%2E%22">Mahler, G.J.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+P%2E%22">Huang, P.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Murray%2C+B%2ET%2E%22">Murray, B.T.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> bmurray@binghamton.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Theoretical+Biology%22">Journal of Theoretical Biology</searchLink>. Nov2019, Vol. 480, p229-240. 12p.
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  Data: <searchLink fieldCode="DE" term="%22Multiscale+modeling%22">Multiscale modeling</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+microenvironment%22">Tumor microenvironment</searchLink><br /><searchLink fieldCode="DE" term="%22Myofibroblasts%22">Myofibroblasts</searchLink><br /><searchLink fieldCode="DE" term="%22Extracellular+matrix%22">Extracellular matrix</searchLink><br /><searchLink fieldCode="DE" term="%22Tissue+remodeling%22">Tissue remodeling</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+migration%22">Cell migration</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: • An in silico model of endothelial to mesenchymal transformation was created. • The computational model uses a hybrid discrete-continuum approach to mimic an in vitro tumor model. • Demonstrates the effects of EndMT-derived activated fibroblasts on tumor cell migration and proliferation. • Elucidates extracellular matrix stiffness-dependent behavior of tumor cells. • Provides a platform to study interactions of EndMT-derived activated fibroblasts, extracellular matrix, and tumors. Endothelial to mesenchymal transformation (EndMT) is a process in which endothelial cells gain a mesenchymal-like phenotype in response to mechanobiological signals that results in the remodeling or repair of underlying tissue. While initially associated with embryonic development, this process has since been shown to occur in adult tissue remodeling including wound healing, fibrosis, and cancer. In an attempt to understand the role of EndMT in cancer progression and metastasis, we present a multiscale, three-dimensional, in silico model. The model couples tissue level phenomena such as extracellular matrix remodeling, cellular level phenomena such as migration and proliferation, and chemical transport in the tumor microenvironment to mimic in vitro tissue models of the cancer microenvironment. The model is used to study the presence of EndMT-derived activated fibroblasts (EDAFs) and varying substrate stiffness on tumor cell migration and proliferation. The simulations accurately model the behavior of tumor cells under given conditions. The presence of EDAFs and/or an increase in substrate stiffness resulted in an increase in tumor cell activity. This model lays the foundation of further studies of EDAFs in a tumor microenvironment on a cellular and subcellular physiological level. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Journal of Theoretical Biology is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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        Value: 10.1016/j.jtbi.2019.08.012
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        Text: English
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        PageCount: 12
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        Type: general
      – SubjectFull: Tumor microenvironment
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      – SubjectFull: Myofibroblasts
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              Text: Nov2019
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