Reference - Detail
|Author||Shiozaki A, Kudou M, Ichikawa D, Fujiwara H, Shimizu H, Ishimoto T, Arita T, Kosuga T, Konishi H, Komatsu S, Okamoto K, Marunaka Y, Otsuji E.|
|Title||Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor.|
BACKGROUND:Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the expression and activity of ion-transport-related molecules in the CSCs of esophageal squamous cell carcinoma.
METHODS:Cells exhibiting strong aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity were isolated from TE8 cells by fluorescence-activated cell sorting, and CSCs were then generated with the sphere formation assay. The gene expression profiles of CSCs were examined by microarray analysis.
RESULTS:Among TE8 cells, ALDH1A1 messenger RNA and protein levels were higher in CSCs than in non-CSCs. The CSCs obtained were resistant to cisplatin and had the ability to redifferentiate. The results of the microarray analysis revealed that the expression of 50 genes encoding plasma membrane proteins was altered in CSCs, whereas that of several genes related to ion channels, including transient receptor potential vanilloid 2 (TRPV2), was upregulated. The TRPV2 inhibitor tranilast was more cytotoxic at a lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. Furthermore, tranilast significantly decreased the cell population that strongly expressed ALDH1A1 among TE8 cells.
CONCLUSIONS:The results of the present study suggest that TRPV2 is involved in the maintenance of CSCs, and that its specific inhibitor, tranilast, has potential as a targeted therapeutic agent against esophageal squamous cell carcinoma.
|MeSH||Aldehyde Dehydrogenase / metabolism Aldehyde Dehydrogenase 1 Antineoplastic Agents / pharmacology Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Differentiation / drug effects Cell Line, Tumor Cell Proliferation / drug effects Drug Screening Assays, Antitumor / methods Esophageal Neoplasms / genetics Esophageal Neoplasms / metabolism Esophageal Neoplasms / pathology* Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic Gene Knockdown Techniques / methods Humans Molecular Targeted Therapy / methods Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology RNA, Neoplasm / genetics Retinal Dehydrogenase Reverse Transcriptase Polymerase Chain Reaction / methods Spheroids, Cellular / drug effects Spheroids, Cellular / metabolism TRPV Cation Channels / antagonists & inhibitors* TRPV Cation Channels / genetics ortho-Aminobenzoates / pharmacology*|
|Human and Animal Cells||TE-8(RCB2098)|