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07.04.2017 | Original Article—Alimentary Tract

Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor

verfasst von: Atsushi Shiozaki, Michihiro Kudou, Daisuke Ichikawa, Hitoshi Fujiwara, Hiroki Shimizu, Takeshi Ishimoto, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Shuhei Komatsu, Kazuma Okamoto, Yoshinori Marunaka, Eigo Otsuji

Erschienen in: Journal of Gastroenterology | Ausgabe 2/2018

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Abstract

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.

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Titel: Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor
verfasst von: Atsushi Shiozaki
Michihiro Kudou
Daisuke Ichikawa
Hitoshi Fujiwara
Hiroki Shimizu
Takeshi Ishimoto
Tomohiro Arita
Toshiyuki Kosuga
Hirotaka Konishi
Shuhei Komatsu
Kazuma Okamoto
Yoshinori Marunaka
Eigo Otsuji
Publikationsdatum: 07.04.2017
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 2/2018
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-017-1338-x

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Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor