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Cancer Stem Cells of Esophageal Adenocarcinoma are Suppressed by Inhibitors of TRPV2 and SLC12A2.
Shiozaki, Atsushi; Inoue, Hiroyuki; Shimizu, Hiroki; Kosuga, Toshiyuki; Takemoto, Kenichi; Kudou, Michihiro; Ohashi, Takuma; Arita, Tomohiro; Konishi, Hirotaka; Komatsu, Shuhei; Kubota, Takeshi; Fujiwara, Hitoshi; Otsuji, Eigo.
Affiliation
  • Shiozaki A; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. shiozaki@koto.kpu-m.ac.jp.
  • Inoue H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Shimizu H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Kosuga T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Takemoto K; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Kudou M; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Ohashi T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Arita T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Konishi H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Komatsu S; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Kubota T; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Fujiwara H; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
  • Otsuji E; Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ann Surg Oncol ; 30(13): 8743-8754, 2023 Dec.
Article in En | MEDLINE | ID: mdl-37684371
BACKGROUND: The potential of membrane transporters activated in cancer stem cells (CSCs) as new therapeutic targets for cancer is attracting increasing interest. Therefore, the present study examined the expression profiles of ion transport-related molecules in the CSCs of esophageal adenocarcinoma (EAC). METHODS: Cells that highly expressed aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were separated from OE33 cells, a human Barrett's EAC cell line, by fluorescence-activated cell sorting. CSCs were identified based on the formation of tumorspheres. Gene expression profiles in CSCs were examined by a microarray analysis. RESULTS: Among OE33 cells, ALDH1A1 messenger RNA levels were higher in CSCs than in non-CSCs. Furthermore, CSCs exhibited resistance to cisplatin and had the capacity to redifferentiate. The results of the microarray analysis of CSCs showed the up-regulated expression of several genes related to ion channels/transporters, such as transient receptor potential vanilloid 2 (TRPV2) and solute carrier family 12 member 2 (SLC12A2). The cytotoxicities of the TRPV2 inhibitor tranilast and the SLC12A2 inhibitor furosemide were higher at lower concentrations in CSCs than in non-CSCs, and both markedly reduced the number of tumorspheres. The cell population among OE33 cells that highly expressed ALDH1A1 also was significantly decreased by these inhibitors. CONCLUSIONS: Based on the present results, TRPV2 and SLC12A2 are involved in the maintenance of CSCs, and their specific inhibitors, tranilast and furosemide, respectively, have potential as targeted therapeutic agents for EAC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Esophageal Neoplasms / Adenocarcinoma / Antineoplastic Agents Limits: Humans Language: En Journal: Ann Surg Oncol Journal subject: NEOPLASIAS Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Esophageal Neoplasms / Adenocarcinoma / Antineoplastic Agents Limits: Humans Language: En Journal: Ann Surg Oncol Journal subject: NEOPLASIAS Year: 2023 Document type: Article Affiliation country: Country of publication: