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

• Published in: Scientific reports Vol. 9; no. 1; pp. 16378 - 11
• Main Authors: Ieda, Takeshi, Tazawa, Hiroshi, Okabayashi, Hiroki, Yano, Shuya, Shigeyasu, Kunitoshi, Kuroda, Shinji, Ohara, Toshiaki, Noma, Kazuhiro, Kishimoto, Hiroyuki, Nishizaki, Masahiko, Kagawa, Shunsuke, Shirakawa, Yasuhiro, Saitou, Takashi, Imamura, Takeshi, Fujiwara, Toshiyoshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.11.2019; Nature Publishing Group
• Subjects: 14/35; 631/67/1504/1885/1393; 631/67/2321; Animals; Coculture Techniques; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Disease Progression; Epithelial cells; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression; HCT116 Cells; Heterografts; Humanities and Social Sciences; Humans; IL-1β; Inflammation; Inflammation - genetics; Inflammation - pathology; Invasiveness; Luminescent Proteins - genetics; Macrophages; Macrophages - metabolism; Macrophages - pathology; Mesenchyme; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Microenvironments; multidisciplinary; Phenotypes; RAW 264.7 Cells; Recombinant Proteins - genetics; Rectum; Red Fluorescent Protein; Science; Science (multidisciplinary); Spatio-Temporal Analysis; Tumor Microenvironment - genetics; Tumor necrosis factor-α; Tumors; Vimentin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-52816-z

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.