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Three-dimensional (3D) cell culture systems have gained increasing interest not only for 3D migration studies but also for their use in drug screening, tissue engineering, and ex vivo modeling of metastatic behavior in the field of cancer biology and morphogenesis in the field of developmental biology. The goal of studying cells in a 3D context is to attempt to more faithfully recapitulate the physiological microenvironment of tissues, including mechanical and structural parameters that we envision will reveal more predictive data for development programs and disease states. In this review, we discuss the pros and cons of several well-characterized 3D cell culture systems for performing 3D migration studies. We discuss the intracellular and extracellular signaling mechanisms that govern cell migration. We also describe the mathematical models and relevant assumptions that can be used to describe 3D cell movement.
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