Microfabricated systems for studying cancer metastasis
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Cancer metastasis is the critical event leading to 90% of cancer related death. Although significant improvement in our understanding on cancer metastasis has been made through years of research, the fundamental mechanism behind this process is still not fully elucidated. For cancer researchers, the “gold standard” for metastasis studies has traditionally been the use of tissue culture and mouse models. Tissue culture offers the simplest system and ease of control but is not able to recapitulate many of the features found in an in vivo tumor microenvironment. On the other hand, mouse model systems offer the most sophisticated and physiologically relevant platforms for studying cancer. However, the lack of control over the in vivo environment in these mouse models and inherent discrepancies from human physiology make results from these models difficult to be translated to clinical trials. The advancement in microfabrication techniques and cancer models developed based on these techniques has shown potential in addressing the gap between in vitro tissue culture and mouse models. Microscopic tumor microenvironments could be built in these in vitro systems to study behavior of human cancer cells. However, the expertise involved in and extra instrumentation needed for implementing these systems have prevented their widespread use by general cancer researchers. In this dissertation, we developed two simple microfabricated systems and demonstrated their application in two aspects of cancer research. The first system is a microfabricated cell patterning stencil, where paracrine signaling can be established and its impact can be measured based on cell migration. Using this tool, we investigated the interaction between melanoma and microenvironmental cells from their common metastasis target organ. Through these simple patterning techniques, we observed significant effects that a given microenvironmental cell line had on the two different melanoma lines, as well as how melanoma affected different microenvironmental cell lines. The second system, a microfluidic device, is able to present individual soluble factors to cancer cells in order to test the response of cancer cells to these physiologically relevant factors. Through this stand-alone system, we found that breast cancer metastasis is influenced by the protein molecules secreted by themselves as well as the local glucose level. Through these findings we believe that our microfabricated systems can benefit the general cancer research community in which a complicated problem can be broken down into manageable pieces and studied on a simple platform in a controlled way. Observation made through these systems can inspire general cancer researchers to form new hypotheses and eventually lead to new findings.