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Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7

The identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with t...

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Autores principales: Seyama, Yusuke, Sudo, Kazuhiro, Hirose, Suguru, Hamano, Yukako, Yamada, Takeshi, Hiroyama, Takashi, Sasaki, Ryosuke, Hirai, Masami Yokota, Hyodo, Ichinosuke, Tsuchiya, Kiichiro, Nakamura, Yukio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587214/
https://www.ncbi.nlm.nih.gov/pubmed/37610679
http://dx.doi.org/10.1007/s13577-023-00967-7
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author Seyama, Yusuke
Sudo, Kazuhiro
Hirose, Suguru
Hamano, Yukako
Yamada, Takeshi
Hiroyama, Takashi
Sasaki, Ryosuke
Hirai, Masami Yokota
Hyodo, Ichinosuke
Tsuchiya, Kiichiro
Nakamura, Yukio
author_facet Seyama, Yusuke
Sudo, Kazuhiro
Hirose, Suguru
Hamano, Yukako
Yamada, Takeshi
Hiroyama, Takashi
Sasaki, Ryosuke
Hirai, Masami Yokota
Hyodo, Ichinosuke
Tsuchiya, Kiichiro
Nakamura, Yukio
author_sort Seyama, Yusuke
collection PubMed
description The identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with tumor-forming activity are enriched in cancer stem cell-like CD13(+)CD166(−) cells and this cell population gradually decreases during culture in conventional culture medium (RPMI1640 containing 10% fetal bovine serum). When Li-7 cells are cultured in mTeSR1, a medium developed for human pluripotent stem cells, CD13(+)CD166(−) cells, and their tumorigenicity is maintained. Here, we sought to identify the mechanisms of tumorigenicity in this sub-population. We compared gene expression profiles of CD13(+)CD166(−) cells with other cell sub-populations and identified nine overexpressed genes (ENPP2, SCGN, FGFR4, MCOLN3, KCNJ16, SMIM22, SMIM24, SERPINH1, and TMPRSS2) in CD13(+)CD166(−) cells. After transfer from mTeSR1 to RPMI1640 containing 10% fetal bovine serum, the expression of these nine genes decreased in Li-7 cells and they lost tumorigenicity. In contrast, when these genes of Li-7 cells were forcibly expressed in cultures using RPMI1640 containing 10% fetal bovine serum, Li-7 cells maintained tumorigenicity. A metabolome analysis using capillary electrophoresis–mass spectrometry showed that two metabolic pathways, “Alanine, aspartate and glutamate metabolism” and “Arginine biosynthesis” were activated in cancer stem-cell-like cells. Our analyses here showed potential therapeutic target genes and metabolites for treatment of cancer stem cells in hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13577-023-00967-7.
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spelling pubmed-105872142023-10-21 Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7 Seyama, Yusuke Sudo, Kazuhiro Hirose, Suguru Hamano, Yukako Yamada, Takeshi Hiroyama, Takashi Sasaki, Ryosuke Hirai, Masami Yokota Hyodo, Ichinosuke Tsuchiya, Kiichiro Nakamura, Yukio Hum Cell Research Article The identification and development of therapeutic targets in cancer stem cells that lead to tumor development, recurrence, metastasis, and drug resistance is an important goal in cancer research. The hepatocellular carcinoma cell line Li-7 contains functionally different types of cells. Cells with tumor-forming activity are enriched in cancer stem cell-like CD13(+)CD166(−) cells and this cell population gradually decreases during culture in conventional culture medium (RPMI1640 containing 10% fetal bovine serum). When Li-7 cells are cultured in mTeSR1, a medium developed for human pluripotent stem cells, CD13(+)CD166(−) cells, and their tumorigenicity is maintained. Here, we sought to identify the mechanisms of tumorigenicity in this sub-population. We compared gene expression profiles of CD13(+)CD166(−) cells with other cell sub-populations and identified nine overexpressed genes (ENPP2, SCGN, FGFR4, MCOLN3, KCNJ16, SMIM22, SMIM24, SERPINH1, and TMPRSS2) in CD13(+)CD166(−) cells. After transfer from mTeSR1 to RPMI1640 containing 10% fetal bovine serum, the expression of these nine genes decreased in Li-7 cells and they lost tumorigenicity. In contrast, when these genes of Li-7 cells were forcibly expressed in cultures using RPMI1640 containing 10% fetal bovine serum, Li-7 cells maintained tumorigenicity. A metabolome analysis using capillary electrophoresis–mass spectrometry showed that two metabolic pathways, “Alanine, aspartate and glutamate metabolism” and “Arginine biosynthesis” were activated in cancer stem-cell-like cells. Our analyses here showed potential therapeutic target genes and metabolites for treatment of cancer stem cells in hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13577-023-00967-7. Springer Nature Singapore 2023-08-23 2023 /pmc/articles/PMC10587214/ /pubmed/37610679 http://dx.doi.org/10.1007/s13577-023-00967-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Seyama, Yusuke
Sudo, Kazuhiro
Hirose, Suguru
Hamano, Yukako
Yamada, Takeshi
Hiroyama, Takashi
Sasaki, Ryosuke
Hirai, Masami Yokota
Hyodo, Ichinosuke
Tsuchiya, Kiichiro
Nakamura, Yukio
Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7
title Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7
title_full Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7
title_fullStr Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7
title_full_unstemmed Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7
title_short Identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line Li-7
title_sort identification of a gene set that maintains tumorigenicity of the hepatocellular carcinoma cell line li-7
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587214/
https://www.ncbi.nlm.nih.gov/pubmed/37610679
http://dx.doi.org/10.1007/s13577-023-00967-7
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