An application of photoactivatable substrate for the evaluation of epithelial-mesenchymal transition inhibitors

Jun Nakanishi; Kenji Sugiyama; Hirotaka Matsuo; Yo Ko Takahashi; Satoshi O. Mura; Takuji Nakashima

doi:10.2116/analsci.18SDP07

An application of photoactivatable substrate for the evaluation of epithelial-mesenchymal transition inhibitors

Jun Nakanishi, Kenji Sugiyama, Hirotaka Matsuo, Yo Ko Takahashi, Satoshi O. Mura, Takuji Nakashima

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

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 celladhesive 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.

Original language	English
Pages (from-to)	65-69
Number of pages	5
Journal	Analytical Sciences
Volume	35
Issue number	1
DOIs	https://doi.org/10.2116/analsci.18SDP07
Publication status	Published - 2019
Externally published	Yes

Keywords

Caged compound
Cancer
Collective cell migration
Drug screening
Epithelial-mesenchymal transition
Leader cells
Mechanobiology
Nanaomycin
Patterning
Transforming growth factor β

ASJC Scopus subject areas

Analytical Chemistry

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title = "An application of photoactivatable substrate for the evaluation of epithelial-mesenchymal transition inhibitors",

abstract = "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 celladhesive 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.",

keywords = "Caged compound, Cancer, Collective cell migration, Drug screening, Epithelial-mesenchymal transition, Leader cells, Mechanobiology, Nanaomycin, Patterning, Transforming growth factor β",

author = "Jun Nakanishi and Kenji Sugiyama and Hirotaka Matsuo and Takahashi, {Yo Ko} and Mura, {Satoshi O.} and Takuji Nakashima",

note = "Funding Information: This study was supported in part by the Japan Society for Promotion of Science, Kakenhi (No. 18H02010 and 18K19946). We thank to Prof. Kazuo Yamaguchi (Kanagawa Univ.) for the photocleavable disulfide molecule.",

year = "2019",

doi = "10.2116/analsci.18SDP07",

language = "English",

volume = "35",

pages = "65--69",

journal = "Analytical Sciences",

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AU - Nakanishi, Jun

AU - Sugiyama, Kenji

AU - Matsuo, Hirotaka

AU - Takahashi, Yo Ko

AU - Mura, Satoshi O.

AU - Nakashima, Takuji

N1 - Funding Information: This study was supported in part by the Japan Society for Promotion of Science, Kakenhi (No. 18H02010 and 18K19946). We thank to Prof. Kazuo Yamaguchi (Kanagawa Univ.) for the photocleavable disulfide molecule.

PY - 2019

Y1 - 2019

N2 - 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 celladhesive 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.

AB - 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 celladhesive 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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KW - Mechanobiology

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KW - Patterning

KW - Transforming growth factor β

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An application of photoactivatable substrate for the evaluation of epithelial-mesenchymal transition inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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