Esophageal Cancer Stem Cells Are Suppressed by Tranilast, a TRPV2 Channel Inhibitor

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2017 Apr 9

PMID 28389731

Citations 33

Authors

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

Affiliations

Soon will be listed here.

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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Shiozaki A, Inoue H, Shimizu H, Kosuga T, Takemoto K, Kudou M Ann Surg Oncol. 2023; 30(13):8743-8754.

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