University of Birmingham > Talks@bham > Applied Mathematics Seminar Series > Mechanistic Analysis of Invasive Patterning in Squamous Cell Carcinoma

Mechanistic Analysis of Invasive Patterning in Squamous Cell Carcinoma

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Many different patterns of collective invasion of cancer cells are observed in tumours. These include ‘single-file’ invading strands, thicker strands, and broad ‘pushing fronts’. How these varying patterns develop and their molecular determinants remain poorly understood. We use complementary experimental and computational approaches to investigate how interactions between cancer cells, cancer associated fibroblasts (CAFs) and the extracellular matrix (ECM) affect the invasion patterns of squamous cell carcinoma (SCC). We have used Cellular Potts modelling to explore parameter space to determine the key mechanistic factors driving patterns of collective invasion. This analysis revealed interesting and unexpected roles of cell-cell adhesion and matrix proteolysis in determining the pattern of collective SCC cell invasion. To test the veracity of these predictions we used two experimental setups: the organotypic assay and the spheroid assay with A431 SCC cells and vulval CAFs. Crispr/Cas KO technology was used to manipulate molecules that determine the cell-cell and cell-matrix adhesion, and proteolysis. The results revealed the importance of matrix degradation for determining the width of collectively invading strands. Further, cell-cell adhesion favors invasion when guidance cues are uniform, but hinders invasion when guidance cues are disparate.

This talk is part of the Applied Mathematics Seminar Series series.

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