The development of cancer-stem cells-targeted hypotoic therapies under the regulation of calsium ion tranporter

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17659
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Takemoto Kenichi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40826038)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / 癌幹細胞 / イオン輸送体 / カルシウムチャネル

Outline of Final Research Achievements

Cancer stem cells　(CSCs) were isolated from colon cancer cell lines, and then the gene expression of CSCs were analyzed by the micro-array method. The results showed that Voltage-gated calcium channel (VGCC) overexpressed CSCs. Previous studies reported that VGCC are associated with cell volume regulation under hypotoniciy; therefore, cell volume and cell viability of CSCs and nomarl cancer cells (NSCs) were evaluated.　The regulatory volume decrease was observed in NCSs; however, the cells ruptured under severe hypotonicity. Cell volume increase under hypotonicity was suppressed in CSCs, moreover, CSCs survived under severe conditions. Potassium and water channel inhibitor suppressed cell volume change of CSCs under hypotonicity. The overall results suggested that CSCs had the resistance of hypotonicity, and the VGCC in CSCs can be therapeutic target.

Free Research Field

癌幹細胞

Academic Significance and Societal Importance of the Research Achievements

大腸癌幹細胞に対する標的治療は再発予防や、治療抵抗性などの回避を目指し研究が盛んに行われており、今回我々が発見したVGCCや、低浸透圧刺激に対する耐性は、標的治療の開発を行う上での契機となる可能性がある。VGCCを標的とした薬剤の投与や、癌幹細胞のイオン輸送体阻害下で低浸透圧刺激を加える手法で癌細胞特異的治療が可能となれば、新たな制癌治療の開発につながると考えられる。