Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-kappaB/HIF-1alpha pathway.

Title

Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-kappaB/HIF-1alpha pathway.

Creator

Lai Fo-Bao; Liu Wen-Ting; Jing Ying-Ying; Yu Guo-Feng; Han Zhi-Peng; Yang Xue; Zeng Jian-Xing; Zhang Hang-Jie; Shi Rong-Yu; Li Xiao-Yong; Pan Xiao-Rong; Li Rong; Zhao Qiu-Dong; Wu Meng-Chao; Zhang Ping; Liu Jing-Feng; Wei Li-Xin

Publisher

Cancer letters

Date

2016
2016-08

Description

Due to the existence of cancer stem cells (CSCs), persistence and relapse of human hepatocellular carcinoma (HCC) are common after treatment with existing anti-cancer therapies. Emerging evidence indicates that lipopolysaccharide (LPS) plays a crucial role in aggravating HCC, but information about the effect of LPS on CSCs of HCC remains scant. Here, we report that the stemness of CD133(+) CSCs sorted from the human HCC cell line Huh7 was maintained well when cells were cultured with LPS. The reduction of CD133 expression was much lesser in cultured CSCs in the presence of LPS. In response to LPS stimulation, CSCs showed an increase in their activity of clonogenesis and tumorigenesis. LPS also supported maintaining CSC abilities of migration, invasion, and chemo-resistance. Treatment with HIF-1alpha-specific siRNA significantly reduced CD133 expression by CSCs at both mRNA and protein levels. Further, the expression of HIF-1alpha and CD133 was reduced in LPS-stimulated CSCs when the NF-kappaB inhibitor was added to the cell culture. HIF-1alpha-specific siRNA also effectively counteracted the effect of LPS on maintaining CSC abilities of migration and invasion. These data indicate that LPS, an important mediator in the liver tumor microenvironment, supports the maintenance of CSC stemness through signaling of the NF-kappaB/HIF-1alpha pathway. Our current study highlights LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC.

Subject

*Cancer stem cells; *Lipopolysaccharide; *Plasticity; *Stemness maintenance; *Tumor microenvironment; AC133 Antigen/genetics/*metabolism; alpha Subunit/genetics/*metabolism; Animals; Antineoplastic Agents – Pharmacodynamics; Antineoplastic Agents/pharmacology; Body Weights and Measures; Carcinoma; Cell Line; Cell Movement – Drug Effects; Cell Movement/drug effects; Cell Physiology; Cell Physiology – Drug Effects; Cell Proliferation/drug effects; Drug Resistance; Gene Expression Regulation; Genes; Genetic Techniques; Hepatocellular; Hepatocellular – Drug Therapy; Hepatocellular – Metabolism; Hepatocellular – Pathology; Hepatocellular/drug therapy/genetics/*metabolism/pathology; Humans; Hypoxia-Inducible Factor 1; Inbred BALB C; Lipopolysaccharides – Pharmacodynamics; Lipopolysaccharides/*pharmacology; Liver Neoplasms; Liver Neoplasms – Drug Therapy; Liver Neoplasms – Metabolism; Liver Neoplasms – Pathology; Liver Neoplasms/drug therapy/genetics/*metabolism/pathology; Male; Mice; Neoplasm; Neoplasm Invasiveness; Neoplastic; Neoplastic Stem Cells/*drug effects/metabolism/pathology; NF-kappa B – Metabolism; NF-kappa B/*metabolism; Nude; Phenotype; Proteins; Proteins – Metabolism; RNA Interference; Signal Transduction – Drug Effects; Signal Transduction/drug effects; Stem Cells – Drug Effects; Stem Cells – Metabolism; Stem Cells – Pathology; Time Factors; Transfection; Tumor Burden; Tumor Microenvironment

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

131–141

Issue

2

Volume

378

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Citation

Lai Fo-Bao; Liu Wen-Ting; Jing Ying-Ying; Yu Guo-Feng; Han Zhi-Peng; Yang Xue; Zeng Jian-Xing; Zhang Hang-Jie; Shi Rong-Yu; Li Xiao-Yong; Pan Xiao-Rong; Li Rong; Zhao Qiu-Dong; Wu Meng-Chao; Zhang Ping; Liu Jing-Feng; Wei Li-Xin, “Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-kappaB/HIF-1alpha pathway.,” NEOMED Bibliography Database, accessed January 25, 2021, https://neomed.omeka.net/items/show/3512.

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