(5u) Novel Experimental Models for Cancer Research and Their Applications

The tremendous challenges in understanding and treating cancer are addressed more effectively through multidisciplinary research, in which bioengineering can contribute significantly. This presentation focuses on hardware and software I have designed to model specific aspects of tumor biology. These systems emphasize three-dimensional substrates, long term cell culture under physiologic conditions, automation, and compatibility with time-lapse imaging and cellular and molecular analyses. Specifically, a fully automated system that tracks cellular motion in 3D with parallel statistical analysis of the cell trajectories enabled measurements of the migratory and invasive potential of tumor cells, and can be used as a screening tool for cancer motility and potentially therapeutic drugs. Another device, the cell-pressor, simulates the stress built-up in a growing tumor and allows quantification of the effects of mechanical compression on cancer cell morphology, metastatic potential and in vivo aggressiveness. Another chamber for time-lapse topography and laser capture microdissection in differentiating living 3D cultures, led to identifying via genomics and proteomics analyses, a set of molecules that could enable autopoiesis of vascular-like networks of tumor cells with potentially significant clinical implications, such as response to anti-angiogenic treatments. The systems used independently or in tandem, enable novel insights into the individual roles and interplay between tumor cell phenotypic plasticity and structural and mechanochemical components of the microenvironment in the process of cancer metastasis.