Computational modeling of cellular dynamics in tumor cell migration
Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.
- Burger, G.A.
- 01 December 2022
- Thesis in Leiden Repository
In this thesis, we studied these mechanisms using mathematical and computational approaches.First, we summarized and reviewed previous computational approaches that have been used to decipher EMP regulation. We then created mathematical models to explore (1) how different regulatory networks can explain epithelial-mesenchymal transition (EMT) in different cell contexts, and (2) how EMP and immune regulation can interact to cause tumor immunoevasion.Next, we studied the role of cell density in migration characteristics of triple-negative breast cancer cell lines by using a combined experimental and computational approach. We show how clustering and pseudopodial dynamics, potentially influenced by EMT-related factors, can alter the migratory behavior of these cell lines.Jointly, our work has shown that computational modeling can be used to test hypotheses based on experimental data, and generate testable hypotheses, making it a valuable addition to wet-lab experiments. Importantly, we identified mechanisms related to potential therapeutic targets, hopefully leading to improved targeted therapies and reduced cancer mortality.