Hepatic stellate cells activated by acidic tumor microenvironment promote the metastasis of hepatocellular carcinoma via osteopontin

Highlights • Tumor acidification aggravates the activation of HCC-infiltrating HSCs. • The activation of HSCs under acidity is dependent on the phosphorylation of ERK. • Acidity-activated HSCs contribute to the metastasis of HCC. • Elevated secreted OPN of acidity-activated HSCs promotes the metasta...

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Veröffentlicht in:	Cancer letters 2015-01, Vol.356 (2), p.713-720
Hauptverfasser:	Song, Jin, Ge, Zhouhong, Yang, Xinrong, Luo, Qin, Wang, Cun, You, Haiyan, Ge, Tianxiang, Deng, Yun, Lin, Hechun, Cui, Yongqi, Chu, Wei, Yao, Ming, Zhang, Zhigang, Gu, Jianren, Fan, Jia, Qin, Wenxin
Format:	Artikel
Sprache:	eng
Schlagworte:	Acidic tumor microenvironment Acidification Acids - chemistry Animals Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Blotting, Western Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - mortality Carcinoma, Hepatocellular - secondary Cell Movement Cell Proliferation Culture Media, Conditioned - pharmacology Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique Gene expression Gene Expression Profiling Glycolysis Hematology, Oncology and Palliative Medicine Hepatic stellate cells Hepatic Stellate Cells - metabolism Hepatic Stellate Cells - pathology Hospitals Humans Hydrogen-Ion Concentration Immunoenzyme Techniques Liver cancer Liver cirrhosis Liver Neoplasms - metabolism Liver Neoplasms - mortality Liver Neoplasms - pathology Medical prognosis Metabolism Metastasis Mice Mice, Inbred BALB C Mice, Nude Myofibroblasts - metabolism Myofibroblasts - pathology Osteopontin - genetics Osteopontin - metabolism Proton pump inhibitor Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Tumor Cells, Cultured Tumor Microenvironment Xenograft Model Antitumor Assays
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Zusammenfassung:	Highlights • Tumor acidification aggravates the activation of HCC-infiltrating HSCs. • The activation of HSCs under acidity is dependent on the phosphorylation of ERK. • Acidity-activated HSCs contribute to the metastasis of HCC. • Elevated secreted OPN of acidity-activated HSCs promotes the metastasis of HCC. • OPN shows prognosis significance, combination with HSCs activation marker α-SMA. • Acidic tumor microenvironment represents a novel mechanism for HCC metastasis and provides a potential therapeutic strategy.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2014.10.021