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Identification of Tumor Initiating Cells with a Small‐Molecule Fluorescent Probe by Using Vimentin as a Biomarker
Authors:Dr Yong‐An Lee  Dr Jong‐Jin Kim  Dr Jungyeol Lee  Jia Hui Jane Lee  Dr Srikanta Sahu  Dr Haw‐Young Kwon  Dr Sung‐Jin Park  Se‐Young Jang  Dr Jun‐Seok Lee  Dr Zhenxun Wang  Dr Wai Leong Tam  Dr Bing Lim  Dr Nam‐Young Kang  Prof Young‐Tae Chang
Institution:1. Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore, Singapore;2. Department of Chemistry, Pohang University of Science and Technology, Pohang, Korea;3. Present address: New drug discovery center, DGMIF, Daegu, Korea;4. Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, Singapore;5. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore;6. Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang, Korea;7. Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, Korea;8. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore;9. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;10. Present address: Merck Sharp and Dohme Translational Medicine Research Center, Singapore, Singapore
Abstract:Tumor initiating cells (TICs) have been implicated in clinical relapse and metastasis of a variety of epithelial cancers, including lung cancer. While efforts toward the development of specific probes for TIC detection and targeting are ongoing, a universal TIC probe has yet to be developed. We report the first TIC‐specific fluorescent chemical probe, TiY, with identification of the molecular target as vimentin, a marker for epithelial‐to‐mesenchymal transition (EMT). TiY selectively stains TICs over differentiated tumor cells or normal cells, and facilitates the visualization and enrichment of functionally active TICs from patient tumors. At high concentration, TiY also shows anti‐TIC activity with low toxicity to non‐TICs. With the unexplored target vimentin, TiY shows potential as a first universal probe for TIC detection in different cancers.
Keywords:antitumor agents  biomarkers  cancer  fluorescent probes  high-throughput screening
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