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. |
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| 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] |
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| Database: | Engineering Source |
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