Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models
Abstract Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousand...
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| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-76312-1 |
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| author | Sun Young Kim Jinhyeon Kim Hajung Kim Young-Tae Chang Hwa-Young Kwon Jong Lyul Lee Yong Sik Yoon Chan Wook Kim Seung-Mo Hong Jin-ho Shin Seung Wook Hong Sung Wook Hwang Byong Duk Ye Jeong-Sik Byeon Suk-Kyun Yang Byung Ho Son Seung-Jae Myung |
| author_facet | Sun Young Kim Jinhyeon Kim Hajung Kim Young-Tae Chang Hwa-Young Kwon Jong Lyul Lee Yong Sik Yoon Chan Wook Kim Seung-Mo Hong Jin-ho Shin Seung Wook Hong Sung Wook Hwang Byong Duk Ye Jeong-Sik Byeon Suk-Kyun Yang Byung Ho Son Seung-Jae Myung |
| author_sort | Sun Young Kim |
| collection | DOAJ |
| description | Abstract Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC. |
| format | Article |
| id | doaj-art-c4d3bd942f6341eb8fc0d611fbc67c20 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c4d3bd942f6341eb8fc0d611fbc67c202024-11-10T12:23:59ZengNature PortfolioScientific Reports2045-23222024-11-0114111310.1038/s41598-024-76312-1Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical modelsSun Young Kim0Jinhyeon Kim1Hajung Kim2Young-Tae Chang3Hwa-Young Kwon4Jong Lyul Lee5Yong Sik Yoon6Chan Wook Kim7Seung-Mo Hong8Jin-ho Shin9Seung Wook Hong10Sung Wook Hwang11Byong Duk Ye12Jeong-Sik Byeon13Suk-Kyun Yang14Byung Ho Son15Seung-Jae Myung16Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of MedicineAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of MedicineAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of MedicineDepartment of Chemistry, Pohang University of Science and Technology (POSTECH)Department of Chemistry, Pohang University of Science and Technology (POSTECH)Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of MedicineDivision of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of MedicineDivision of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of MedicineDigestive Diseases Research Center, University of Ulsan College of MedicineDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineDigestive Diseases Research Center, University of Ulsan College of MedicineDigestive Diseases Research Center, University of Ulsan College of MedicineDigestive Diseases Research Center, University of Ulsan College of MedicineDigestive Diseases Research Center, University of Ulsan College of MedicineDepartment of Gastroenterology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Surgery, Asan Medical Center, University of Ulsan College of MedicineAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of MedicineAbstract Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC.https://doi.org/10.1038/s41598-024-76312-1Fluorescence-guided tumor imagingColorectal cancerTumor-initiating probe yellowEpithelial-mesenchymal transition |
| spellingShingle | Sun Young Kim Jinhyeon Kim Hajung Kim Young-Tae Chang Hwa-Young Kwon Jong Lyul Lee Yong Sik Yoon Chan Wook Kim Seung-Mo Hong Jin-ho Shin Seung Wook Hong Sung Wook Hwang Byong Duk Ye Jeong-Sik Byeon Suk-Kyun Yang Byung Ho Son Seung-Jae Myung Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models Scientific Reports Fluorescence-guided tumor imaging Colorectal cancer Tumor-initiating probe yellow Epithelial-mesenchymal transition |
| title | Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models |
| title_full | Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models |
| title_fullStr | Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models |
| title_full_unstemmed | Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models |
| title_short | Fluorescence-guided tumor visualization of colorectal cancer using tumor-initiating probe yellow in preclinical models |
| title_sort | fluorescence guided tumor visualization of colorectal cancer using tumor initiating probe yellow in preclinical models |
| topic | Fluorescence-guided tumor imaging Colorectal cancer Tumor-initiating probe yellow Epithelial-mesenchymal transition |
| url | https://doi.org/10.1038/s41598-024-76312-1 |
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