Expression and activity of ion transporters in pancreatic cancer stem cells.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10710
• 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: Toma Atsushi 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30516191)
• 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) ; 塩崎 敦 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40568086)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 膵癌

Outline of Final Research Achievements

Cells exhibiting strong ALDH1 activity were isolated from PK59 pancreatic cancer cells by cell sorting, and cancer stem cells (CSCs) were then generated with the sphere formation assay. The gene expression profiles of CSCs were examined by microarray analysis, and the expression of 57 genes related to ion channels, including voltage-gated potassium channel (Kv), was upregulated. The Kv inhibitor, 4-aminopyridine (4-AP) was more cytotoxic at a lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. Furthermore, 4-AP significantly decreased the cell population that strongly expressed ALDH1 among PK59 cells. In a xenograft model in nude mice, injection of PK59 cells treated with 4-AP resulted in significantly smaller tumor volumes than those of nontreated cells. These results suggest that Kv is involved in the maintenance of CSCs, and that its specific inhibitor, 4-AP, has potential as a targeted therapeutic agent against pancreatic carcinoma.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

電位依存性カリウムチャネルが膵癌幹細胞において高発現し、その阻害剤である4-aminopyridine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。4-aminopyridineは多発性硬化症に対し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。