RRC ID 62247
著者 Song J, Ge Z, Yang X, Luo Q, Wang C, You H, Ge T, Deng Y, Lin H, Cui Y, Chu W, Yao M, Zhang Z, Gu J, Fan J, Qin W.
タイトル Hepatic stellate cells activated by acidic tumor microenvironment promote the metastasis of hepatocellular carcinoma via osteopontin.
ジャーナル Cancer Lett
Abstract Extracellular pH of solid tumor is generally acidic due to excessive glycolysis and poor perfusion. But whether acidic tumor microenvironment influenced the stromal cells infiltrating in tumor remains unknown. As the predominant progenitor of stromal cells in liver, the number of activated hepatic stellate cells (HSCs) was found positively correlated to the acidification level in the tumor tissues of HCC patients in our study. Whereas, in vitro acidic culture condition and in vivo co-implanting xenograft model were adopted to study the response of HSCs and its influence on HCC progression. HSCs were activated under acidic culture condition depending on the phosphorylation of cellular signal-regulated kinase (ERK). Acidity-activated HSCs promoted HCC metastasis in vitro and in vivo. Osteopontin (OPN) excretion from HSCs was increased under acidic condition and proved to promote the migration of HCC cells. Furthermore, the expression level of OPN was significantly associated with myofibroblasts and the combination of α-SMA with OPN was a powerful predictor for poor prognosis of HCC patients. Activation of HSCs in acidic tumor microenvironment represents a novel mechanism for HCC metastasis and provides a potential therapeutic strategy for HCC.
巻・号 356(2 Pt B)
ページ 713-20
公開日 2015-1-28
DOI 10.1016/j.canlet.2014.10.021
PII S0304-3835(14)00620-X
PMID 25449435
MeSH 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 Profiling Hepatic Stellate Cells / metabolism Hepatic Stellate Cells / pathology* Humans Hydrogen-Ion Concentration Immunoenzyme Techniques Liver Neoplasms / metabolism Liver Neoplasms / mortality Liver Neoplasms / pathology* Mice Mice, Inbred BALB C Mice, Nude Myofibroblasts / metabolism Myofibroblasts / pathology* Osteopontin / genetics Osteopontin / metabolism* RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Tumor Microenvironment* Xenograft Model Antitumor Assays
IF 7.36
リソース情報
ヒト・動物細胞 HuH-7