Abstract

The acquisition of invasive behaviour enables the tumour cells to move into either the surrounding tissue or the vasculature and thereby spread to other parts of the body. To study cell motility in tumours we perform intravital multi-photon confocal imaging of tumours in anaesthetised mice. Cell migration depends on the complex interplay of actin polymerisation, deformation of the plasma membrane, actomyosin contractility, and cell-matrix adhesion. Recent work has revealed that cancer cells can use different migratory strategies, particularly when challenged with complex three-dimensional matrices in vivo. Further the mode of cell migration determines the sensitivity of invading cancer cells to interventions that target either regulators of actin polymerisation or actomyosin contractility. This presents a particular problem when attempting to extrapolate findings from simple in vitro experiments to the complex matrix environments that surround tumours. To address this we have developed an agent based-finite element model of cell motility within different ECM topologies. This enables the optimal migration strategy and response to anti-invasive agents in different matrix geometries to be predicted. We then test these predictions by intravital imaging of melanoma.