Dynamic imaging of plasticity and escape in tumor cell invasion

Cancer cell interactions with the extracellular matrix and the migration therein require adhesion and traction provided by integrins, together with pericellular proteolysis executed by extracellular matrix degrading proteases. We have used experimental interference strategies and identified plasticity of migration modes resulting in new ways of dissemination. As imaged by three-dimensional matrix-based models and intravital microscopy, quantitative reconstruction from movies has shown how tumor cells depend on adhesion mechanisms but continue to migrate after adhesion receptors are blocked, has shown how proteases generate proteolytic tracks but are dispensable if 'physical' strategies allow cells to bypass tissue barriers, and has shown why individual and collective invasion patters predispose to a different outcome after pharmacotherapeutic intervention.

These findings have implications with reference to invasion as a therapeutic target in progressive cancer disease.