Expression and role of TRPV2 in esophageal squamous cell carcinoma and cancer stem cells.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shiozaki Atsushi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40568086)
• Co-Investigator(Kenkyū-buntansha): 大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 食道癌

Outline of Final Research Achievements

Cells exhibiting strong ALDH1A1 activity were isolated from TE4 and TE8 esophageal squamous cell carcinoma (ESCC) cells by cell sorting, and cancer stem cells (CSCs) were generated with the sphere formation assay. Microarray analysis revealed TRPV2 was upregulated in CSCs, and its inhibitor tranilast effectively decreased the number of tumorspheres. An immunohistochemical analysis revealed a relationship between strong TRPV2 expression and a poor prognosis in ESCC patients. TRPV2 was overexpressed in TE15 and KYSE170 cells, and TRPV2 depletion with siRNA suppressed cell proliferation, cell cycle progression, and invasion/migration, and induced apoptosis. A pathway analysis of microarray data revealed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes. These results provide an insight into the role of TRPV2 as a biomarker, and that its specific inhibitor, tranilast, has potential as a targeted therapeutic agent against ESCC.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

TRPV2が食道扁平上皮癌幹細胞において高発現し、その阻害剤であるトラニラストが癌幹細胞特異的に抑制効果を示すことを新たに見出した。トラニラストは抗アレルギー剤、ケロイド・肥厚性瘢痕の予防・治療薬として臨床で用いられている薬剤であり、その抗腫瘍効果を明らかにしたことの社会的意義は大きいと考えられる。また、TRPV2のWnt/β-カテニンシグナル伝達系を介する新たな腫瘍進展制御機構や、予後因子としての意義を明らかにし、バイオマーカーや治療標的としての可能性を示した。