Computational Modeling of Metastatic Cancer Cell Migration through a Remodeling Extracellular Matrix

Fig. 1 Ford Versypt Lab publication cover article. Dynamics in a metastatic tumor microenvironment. Panels from left to right: (1) The basement membrane around the edge of the primary tumor (cluster of cancer cells in red) has already been perforated by cancer cells. The surrounding collagen fibers are randomly oriented in the ECM. (2) Enzymes MMP and LOX are secreted by cancer cells to degrade and cross-link collagen fibers. MMP generates spaces for cancer cells to begin detaching away from the primary tumor mass to invade the ECM. (3) Meanwhile, aligned and cross-linked collagen fibers form a fibrous pathway along which cancer cells prefer to travel. (4) Collagen fibers continue to be cross-linked to aid the maneuvers of cancer cells further through the matrix.

Overview

The prognosis is grim for patients who have metastasis, where cancer cells spread from a localized tumor to other regions in the body. Cancer cells and the surrounding extracellular matrix (ECM) interact to facilitate migration of cancer cells during early metastasis. Cancer cells secrete particular enzymes to cut and align collagen fibers of the ECM. These ECM remodeling activities transform the ECM from a random fiber matrix into an oriented "fibrous highway" that enhances cancer cell migration. The Ford Versypt lab addresses remodeling of the ECM during metastasis and the impacts on cellular migration through dynamic heterogeneous ECM biomaterials. Hybrid partial differential equation and agent-based modeling approaches are used to predict the interactions in tumor microenvironments.

Resulting Publications

Y. T. Nguyen Edalgo, A. L. Zornes, and A. N. Ford Versypt, A Hybrid Discrete-Continuous Model of Metastatic Cancer Cell Migration through a Remodeling Extracellular Matrix, AIChE Journal, 65(9), e16671, 2019. DOI: 10.1002/aic.16671
Y. T. Nguyen Edalgo and A. N. Ford Versypt, Mathematical Modeling of the Metastatic Cancer Migration through a Remodeling Extracellular Matrix, Processes, 6(5), 58, 2018. DOI: 10.3390/pr6050058 Cover article: https://www.mdpi.com/2227-9717/6/5