Biophysical Benchmarks of Malignancy in Primary Breast Tumor Cells

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The process of cancer cell invasion in tissue is poorly understood due to a lack of mechanistic knowledge of underlying physical principles and limited physiological relevance of 3-dimensional (3D) invasion test systems. This proposal will systematically test the hypothesis of a mechanistic link between mechanical properties of primary breast tumor cells and their metastatic potential. Comparing primary patient-derived tumor and normal breast cells in 2D and 3D environments, we will determine the stiffness, shape, protrusion dynamics, mechanotransduction and traction forces of migrating cells. Moreover, we will explore the statistical properties of cell migration and invasion, using a variety of differently stiff, porous and adhesive natural extracellular matrices. Current in vitro extracellular matrix models often give contradictory results and are far from replicating the physiological situation in vivo. Therefore, we will develop 3D cell culture systems with tunable and precisely controllable parameters that will allow us to monitor the invasion of primary breast cancer cells with high-resolution imaging and novel high-throughput methods. We predict significant differences in the biomechanical properties and the invasion behavior between primary tumor cells that have metastasized versus those that have not. These in vitro predictions will be correlated with in vivo clinical findings from the same patient cohort.