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Title:
Sphere-forming culture enriches liver cancer stem cells and reveals Stearoyl-CoA desaturase 1 as a potential therapeutic target | BMC Cancer
Description:
Backgrounds The role of sphere-forming culture in enriching subpopulations with stem-cell properties in hepatocellular carcinoma (HCC) is unclear. The present study investigates its value in enriching cancer stem cells (CSCs) subpopulations and the mechanism by which HCC CSCs are maintained. Methods HCC cell lines and fresh primary tumor cells were cultured in serum-free and ultra-low attachment conditions to allow formation of HCC spheres. In vitro and in vivo experiments were performed to evaluate CSC characteristics. Expression levels of CSC-related genes were assessed by qRT-PCR and the correlation between sphere formation and clinical characteristics was investigated. Finally, gene expression profiling was performed to explore the molecular mechanism underlying HCC CSC maintenance. Results We found that both cell lines and primary tumor cells formed spheres. HCC spheres possessed the capacity for self-renewal, proliferation, drug resistance, and contained different subpopulations of CSCs. Of interest, 500 sphere-forming Huh7 cells or 200 primary tumor cells could generate tumors in immunodeficient animals. Sphere formation correlated with size, multiple tumors, satellite lesions, and advanced stage. Further investigation identified that the PPARα-SCD1 axis plays an important role in maintenance of the CSC properties of HCC sphere cells by promoting nuclear accumulation of β-Catenin. Inhibition of SCD1 interfered with sphere formation, down-regulated expression of CSC-related markers, and reduced β-Catenin nuclear accumulation. Conclusions Sphere-forming culture can effectively enrich subpopulations with stem-cell properties, which are maintained through activation of the PPARα-SCD1 axis. Therefore, we suggest that targeting the SCD1-related CSC machinery might provide a novel insight into HCC treatment.
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Keywords {š}
cells, hcc, sphere, cell, cancer, article, expression, csc, tumor, stem, google, scholar, scd, data, spheres, huh, cas, cscs, sphereforming, fig, properties, parental, carcinoma, hepatocellular, formation, pparα, culture, study, pathway, treatment, analysis, lines, primary, usa, hepb, research, role, found, liver, genes, inhibition, treated, capacity, βcatenin, markers, patients, human, performed, results, potential,
Topics {āļø}
pe-conjugated anti-epcam/anti-cd133 antibodies peroxisome proliferator-activated receptor-alpha xin-rong yang regulating wnt/β-catenin signaling sphere-forming culture enriches stearoyl-coa desaturase stearoyl coa desaturase-1 stearoyl-coa desaturase 1 stem/progenitor cell features maintaining stem-cell phenotypes intrinsic stem-cell properties torsadogenic human ether-a sphere-forming subgroup cells nonparametric mannāwhitney test anchorage-independent sphere culture wnt positive-signaling loop sphere-forming tumor cells wilcoxon signed-rank test ultra-low attachment conditions cancer stem cell cell stem cell article download pdf stem-cell phenotypes efficient sphere-forming capacity human hepatocellular carcinoma kaplanāmeier survival curves treated sphere-forming cells human liver cancer mature hepatocyte-related genes efficient tumor-initiating capacity liver cancer institute β-catenin transcriptional activity mir-130b promotes cd133 cancer stem cells male nod/scid mice recipient nod/scid mice scd1-related csc machinery hepatocellular carcinoma cells tumor-initiating cells contribute liver cancer cells differential expression profiles hepatocellular carcinoma contributes serum-free dmem/matrigel sphere-forming assay stem-cell markers pparα-scd1 axis plays stem-cell properties research ethics committee bai-shen pan cell biology
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headline:Sphere-forming culture enriches liver cancer stem cells and reveals Stearoyl-CoA desaturase 1 as a potential therapeutic target
description:The role of sphere-forming culture in enriching subpopulations with stem-cell properties in hepatocellular carcinoma (HCC) is unclear. The present study investigates its value in enriching cancer stem cells (CSCs) subpopulations and the mechanism by which HCC CSCs are maintained. HCC cell lines and fresh primary tumor cells were cultured in serum-free and ultra-low attachment conditions to allow formation of HCC spheres. In vitro and in vivo experiments were performed to evaluate CSC characteristics. Expression levels of CSC-related genes were assessed by qRT-PCR and the correlation between sphere formation and clinical characteristics was investigated. Finally, gene expression profiling was performed to explore the molecular mechanism underlying HCC CSC maintenance. We found that both cell lines and primary tumor cells formed spheres. HCC spheres possessed the capacity for self-renewal, proliferation, drug resistance, and contained different subpopulations of CSCs. Of interest, 500 sphere-forming Huh7 cells or 200 primary tumor cells could generate tumors in immunodeficient animals. Sphere formation correlated with size, multiple tumors, satellite lesions, and advanced stage. Further investigation identified that the PPARα-SCD1 axis plays an important role in maintenance of the CSC properties of HCC sphere cells by promoting nuclear accumulation of β-Catenin. Inhibition of SCD1 interfered with sphere formation, down-regulated expression of CSC-related markers, and reduced β-Catenin nuclear accumulation. Sphere-forming culture can effectively enrich subpopulations with stem-cell properties, which are maintained through activation of the PPARα-SCD1 axis. Therefore, we suggest that targeting the SCD1-related CSC machinery might provide a novel insight into HCC treatment.
datePublished:2019-08-01T00:00:00Z
dateModified:2019-08-01T00:00:00Z
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keywords:
Cancer stem cell
Hepatocellular carcinoma
Stearoyl-CoA desaturase 1
Sphere-forming assay
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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headline:Sphere-forming culture enriches liver cancer stem cells and reveals Stearoyl-CoA desaturase 1 as a potential therapeutic target
description:The role of sphere-forming culture in enriching subpopulations with stem-cell properties in hepatocellular carcinoma (HCC) is unclear. The present study investigates its value in enriching cancer stem cells (CSCs) subpopulations and the mechanism by which HCC CSCs are maintained. HCC cell lines and fresh primary tumor cells were cultured in serum-free and ultra-low attachment conditions to allow formation of HCC spheres. In vitro and in vivo experiments were performed to evaluate CSC characteristics. Expression levels of CSC-related genes were assessed by qRT-PCR and the correlation between sphere formation and clinical characteristics was investigated. Finally, gene expression profiling was performed to explore the molecular mechanism underlying HCC CSC maintenance. We found that both cell lines and primary tumor cells formed spheres. HCC spheres possessed the capacity for self-renewal, proliferation, drug resistance, and contained different subpopulations of CSCs. Of interest, 500 sphere-forming Huh7 cells or 200 primary tumor cells could generate tumors in immunodeficient animals. Sphere formation correlated with size, multiple tumors, satellite lesions, and advanced stage. Further investigation identified that the PPARα-SCD1 axis plays an important role in maintenance of the CSC properties of HCC sphere cells by promoting nuclear accumulation of β-Catenin. Inhibition of SCD1 interfered with sphere formation, down-regulated expression of CSC-related markers, and reduced β-Catenin nuclear accumulation. Sphere-forming culture can effectively enrich subpopulations with stem-cell properties, which are maintained through activation of the PPARα-SCD1 axis. Therefore, we suggest that targeting the SCD1-related CSC machinery might provide a novel insight into HCC treatment.
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Cancer stem cell
Hepatocellular carcinoma
Stearoyl-CoA desaturase 1
Sphere-forming assay
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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PostalAddress:
name:Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, Peopleās Republic of China
name:Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, Peopleās Republic of China
name:Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Cancer Research Institute, Xiangya School of Medicine, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China
name:Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
name:Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, Peopleās Republic of China
name:Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, Peopleās Republic of China
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