TY - JOUR
T1 - Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment–colorectal cancer network
AU - Ieda, Takeshi
AU - Tazawa, Hiroshi
AU - Okabayashi, Hiroki
AU - Yano, Shuuya
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
N1 - Funding Information:
We thank Tomoko Sueishi and Tae Yamanishi for excellent technical support. We also thank Dr. Masakatsu Yamashita, Dr. Ryosuke Kawakami, and Dr. Sota Takanezawa (Ehime University) for helpful discussions. This study was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan (H. Tazawa, 25462057 and 16K10596; M. Nishizaki, 26461978 and 17K10589; T. Saitou, 16K18578; T. Imamura, 15H04962, 16H06280 “Advanced Bioimaging Support” and 15H05952 “Resonance Bio”; and T. Fujiwara, 16H05416). This work was performed under the Research Program of the “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” at the Network Joint Research Center for Materials and Devices.
Publisher Copyright:
© 2019, The Author(s).
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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U2 - 10.1038/s41598-019-52816-z
DO - 10.1038/s41598-019-52816-z
M3 - Article
C2 - 31705021
AN - SCOPUS:85074714359
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 16378
ER -
