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Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model

BACKGROUND: Cancer stem cells (CSCs) are involved in drug resistance, metastasis, and relapse of cancers, which can significantly affect tumor therapy. Hence, to develop specifically therapeutic target probe at CSCs for improvement of survival and quality of life of cancer patients is urgently neede...

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Autores principales: Guan, Siao-Syun, Wu, Cheng-Tien, Liao, Tse-Zung, Luo, Tsai-Yueh, Lin, Kun-Liang, Liu, Shing-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040160/
https://www.ncbi.nlm.nih.gov/pubmed/32096011
http://dx.doi.org/10.1186/s13550-020-0597-3
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author Guan, Siao-Syun
Wu, Cheng-Tien
Liao, Tse-Zung
Luo, Tsai-Yueh
Lin, Kun-Liang
Liu, Shing-Hwa
author_facet Guan, Siao-Syun
Wu, Cheng-Tien
Liao, Tse-Zung
Luo, Tsai-Yueh
Lin, Kun-Liang
Liu, Shing-Hwa
author_sort Guan, Siao-Syun
collection PubMed
description BACKGROUND: Cancer stem cells (CSCs) are involved in drug resistance, metastasis, and relapse of cancers, which can significantly affect tumor therapy. Hence, to develop specifically therapeutic target probe at CSCs for improvement of survival and quality of life of cancer patients is urgently needed. The CD166 protein has been suggested to be involved in colorectal cancer (CRC) tumorigenesis and to be considered a marker for colorectal CSCs (CRCSCs) detection. In this study, therefore, we attend to apply a nuclear imaging agent probe, Glycine(18)-Cystine-linked CD166-targeted peptides (CD166tp-G(18)C), to detect the changes of CD166 level in a CRC xenograft mouse model. RESULTS: We isolated the CD166-positive cells from the HCT15 CRC cell line (CD166(+)HCT15) and evaluated their morphology and ability of clone formation, migration, protein expression, and drug resistance. The CD166-positive HCT15 cells display the CSCs characteristics. We discovered and designed a CD166-targeted peptide (CD166tp-G(18)C) as a targeted probe of CRC stem-like cell for cell binding assay. The CD166tp-G(18)C confirmed the CD166 protein targeting ability in CD166(+)HCT15 cells. The diethylenetriaminopentaacetic acid (DTPA)-conjugated CD166tp-G(18)C further was labeled with indium-111 ((111)In-DTPA-CD166tp-G(18)C) as nuclear imaging agent for imaging and bio-distribution analysis in vivo. Finally, we observed that the (111)In-DTPA-CD166tp-G(18)C was significantly enhanced in tumor tissues of CD166(+)HCT15 xenograft mice as compared to the non-CD166tp-G(18)C control. CONCLUSIONS: Our results indicated that the indium-111-labeled CD166tp-G(18)C may be served as a powerful tool for colorectal CSCs nuclear imaging in the CRC patients.
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spelling pubmed-70401602020-03-10 Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model Guan, Siao-Syun Wu, Cheng-Tien Liao, Tse-Zung Luo, Tsai-Yueh Lin, Kun-Liang Liu, Shing-Hwa EJNMMI Res Original Research BACKGROUND: Cancer stem cells (CSCs) are involved in drug resistance, metastasis, and relapse of cancers, which can significantly affect tumor therapy. Hence, to develop specifically therapeutic target probe at CSCs for improvement of survival and quality of life of cancer patients is urgently needed. The CD166 protein has been suggested to be involved in colorectal cancer (CRC) tumorigenesis and to be considered a marker for colorectal CSCs (CRCSCs) detection. In this study, therefore, we attend to apply a nuclear imaging agent probe, Glycine(18)-Cystine-linked CD166-targeted peptides (CD166tp-G(18)C), to detect the changes of CD166 level in a CRC xenograft mouse model. RESULTS: We isolated the CD166-positive cells from the HCT15 CRC cell line (CD166(+)HCT15) and evaluated their morphology and ability of clone formation, migration, protein expression, and drug resistance. The CD166-positive HCT15 cells display the CSCs characteristics. We discovered and designed a CD166-targeted peptide (CD166tp-G(18)C) as a targeted probe of CRC stem-like cell for cell binding assay. The CD166tp-G(18)C confirmed the CD166 protein targeting ability in CD166(+)HCT15 cells. The diethylenetriaminopentaacetic acid (DTPA)-conjugated CD166tp-G(18)C further was labeled with indium-111 ((111)In-DTPA-CD166tp-G(18)C) as nuclear imaging agent for imaging and bio-distribution analysis in vivo. Finally, we observed that the (111)In-DTPA-CD166tp-G(18)C was significantly enhanced in tumor tissues of CD166(+)HCT15 xenograft mice as compared to the non-CD166tp-G(18)C control. CONCLUSIONS: Our results indicated that the indium-111-labeled CD166tp-G(18)C may be served as a powerful tool for colorectal CSCs nuclear imaging in the CRC patients. Springer Berlin Heidelberg 2020-02-24 /pmc/articles/PMC7040160/ /pubmed/32096011 http://dx.doi.org/10.1186/s13550-020-0597-3 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Guan, Siao-Syun
Wu, Cheng-Tien
Liao, Tse-Zung
Luo, Tsai-Yueh
Lin, Kun-Liang
Liu, Shing-Hwa
Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
title Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
title_full Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
title_fullStr Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
title_full_unstemmed Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
title_short Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
title_sort indium-111-labeled cd166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040160/
https://www.ncbi.nlm.nih.gov/pubmed/32096011
http://dx.doi.org/10.1186/s13550-020-0597-3
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