Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment–colorectal cancer network

Takeshi Ieda, Hiroshi Tazawa, Hiroki Okabayashi, Shuya Yano, Kunitoshi Shigeyasu, Shinji Kuroda, Toshiaki Ohara, Kazuhiro Noma, Hiroyuki Kishimoto, Masahiko Nishizaki, Shunsuke Kagawa, Yasuhiro Shirakawa, Takashi Saitou, Takeshi Imamura, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

Abstract

Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment–CRC networks.

Original languageEnglish
Article number16378
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Epithelial-Mesenchymal Transition
Colorectal Neoplasms
Neoplasms
Phenotype
Biological Phenomena
Vimentin
Rectal Neoplasms
Interleukin-1
Fluorescence
Epithelial Cells
Macrophages
Cytokines

ASJC Scopus subject areas

  • General

Cite this

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title = "Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment–colorectal cancer network",
abstract = "Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment–CRC networks.",
author = "Takeshi Ieda and Hiroshi Tazawa and Hiroki Okabayashi and Shuya Yano and Kunitoshi Shigeyasu and Shinji Kuroda and Toshiaki Ohara and Kazuhiro Noma and Hiroyuki Kishimoto and Masahiko Nishizaki and Shunsuke Kagawa and Yasuhiro Shirakawa and Takashi Saitou and Takeshi Imamura and Toshiyoshi Fujiwara",
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AU - Ieda, Takeshi

AU - Tazawa, Hiroshi

AU - Okabayashi, Hiroki

AU - Yano, Shuya

AU - Shigeyasu, Kunitoshi

AU - Kuroda, Shinji

AU - Ohara, Toshiaki

AU - Noma, Kazuhiro

AU - Kishimoto, Hiroyuki

AU - Nishizaki, Masahiko

AU - Kagawa, Shunsuke

AU - Shirakawa, Yasuhiro

AU - Saitou, Takashi

AU - Imamura, Takeshi

AU - Fujiwara, Toshiyoshi

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment–CRC networks.

AB - Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment–CRC networks.

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