Thesis Defense in Chemistry
Spatial organization and segregation of cells in breast cancer
Presented by Alexander Devanny, Kaufman Group
Solid tumors comprise a complex mixture of cells, and the biophysical determinants and consequences of their spatial organization are incompletely understood. Here, we use an in vitro model of tumor heterogeneity and a complementary minimal computational model of cell sorting to predict and control spatial organization in aggregates composed of multiple cell types. Cells are found to compact into spheroids either rapidly, driven by cell-adhesion molecules, or slowly, initiated by cell adhesion to extracellular matrix proteins. Simulations accurately replicate the experimental sorting hierarchy and reveal that more adhesive cell types position inside of mixed-cell-type spheroids, with aggressive cancer cells typically positioned at the periphery. Additionally, we show that reducing cellular contractility differentially affects cells that compact rapidly and slowly, allowing for control over spatial organization in mixed spheroids. Positioning aggressive cells at the core of such spheroids reduces invasion, suggesting a potential strategy for containing aggressive cancers.
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