Analytical Sciences

An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors

Jun NAKANISHI,* Kenji SUGIYAMA,* Hirotaka MATSUO,**,*** Yoko TAKAHASHI,** Satoshi OMURA,** and Takuji NAKASHIMA**,***

*International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
**Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato, Tokyo 108-8641, Japan
***Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato, Tokyo 108-8641, Japan

Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to cell-adhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

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