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A hybrid discrete–continuous model of metastatic cancer cell migration through a remodeling extracellular matrix
Authors:Yen T Nguyen Edalgo  Anya L Zornes  Ashlee N Ford Versypt
Affiliation:School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma
Abstract:A major cause of cancer mortality is metastasis of cancer cells from a localized tumor to other parts of the body. The interactions between cancer cells and the surrounding tumor microenvironment, particularly the extracellular matrix (ECM), are central to metastatic migration. During metastasis, enzymes are secreted to degrade and crosslink collagen fibers in the ECM, inducing structural alterations and changes in the properties of the ECM. The mechanism of how these changes facilitate the directional motility of cancer cells along the collagen fibers remains unclear. A hybrid discrete–continuous computational model is developed via the software CompuCell3D to simulate the migration of metastatic cancer cells through the ECM during chemical and physical remodeling. Cancer cells are treated as discrete agents, and ECM components (collagen fibers and remodeling enzymes) are modeled by partial differential equations. The computational model of cancer migration provides understanding of how ECM remodeling affects migration efficiency.
Keywords:CompuCell3D  computational modeling  lysyl oxidase  matrix metalloproteinases  systems biology  tumor microenvironment
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