Basic study of targeting cancer stem cells by heavy-ion beams and hyperthermia

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: Takahashi Akihisa 群馬大学, 重粒子線医学推進機構, 教授 (60275336)
• Research Collaborator: ParK Seong-Joon
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 放射線科学 / 重粒子線 / ハイパーサーミア / がん幹細胞 / 感受性

Outline of Final Research Achievements

Targeting cancer stem cells (CSCs) might enable improvement of the cancer therapies. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of CSC populations. Interestingly, Lin28B-overexpressed melanoma cells were more resistant to X-ray irradiation than control cells, and Lin28B-induced radioresistance was abolished after carbon ion irradiation. Our results suggest that a carbon ion beam is more effective than an X-ray beam in terms of killing cancer cells, possibly due to elimination of CSC populations.
In addition, we demonstrated that C-ion and heat treatment can induce DNA damage via DSB formation reflected by γH2AX foci formation under hypoxia. C-ion and yperthermia therapy can be beneficial for the prognosis of cancer patients through increased DNA damage leading to tumor cell death.

Free Research Field

放射線生物

Academic Significance and Societal Importance of the Research Achievements

従来、「がん幹細胞」は細胞表面マーカーを指標としていたが、それらは数多く存在し。さらに、細胞表面マーカーは一過性に増減するものの、細胞集団内での陽性頻度が一定に保たれていることが報告されており、がん幹細胞化に果たす役割は不明な点が多かった。その点、我々が利用したLin28未分化誘導経路を遺伝子操作したがん細胞を用いることは、本質的な「がん幹細胞」を捉えられる点が学術的な特色があったと言えるだろう。
また、従来のX線治療で抵抗性を示した低酸素分画において、重粒子線と温熱による効率的なDNA損傷生成を確認し、重粒子線と温熱治療のアドバンテージを示す結果を得た。