Inflammatory chemokine CCL2 inhibitor for quiescent eradication of glioma tumor stem cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Hirosaki University
• Principal Investigator: Asano Kenichiro 弘前大学, 医学研究科, 准教授 (90312496)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腫瘍幹細胞 / 駆逐療法 / CCL2阻害剤 / 悪性グリオーマ

Outline of Final Research Achievements

The aim of this study has been to efficiently treat malignant glioma cells by taking advantage of their strong invasive potential to migrate and deposit them in a single location. However, in-vivo experiments showed recurrence, suggesting that the cause was residual stem cell lineage. We developed a stem cell quiescence eradication therapy that sensitizes stem cells in the G0 phase of the CCL2 cascade to anti-cancer drugs while they are out of the G0 phase.
In-vitro, the optimal concentration of 10~100nmol/ml CCL2 inhibitor was confirmed by G1 level of simple flow cytometer, and in-vivo, the tumor immune response was strong as well as the surrounding inflammatory response. The survival time was prolonged, but not significantly different from the previous group.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

悪性グリオーマ細胞の性質を逆手にとった治療法の開発である。浸潤性性格を利用し吸着療法をおこない、抗腫瘍薬や放射線の効果が期待できないG0腫瘍休止期をCCL2阻害剤で感受性のある細胞回転期に駆逐して腫瘍根絶を狙う新機軸の治療法である。結果として生命予後の延長が見られているが、有為差は得られなかった。原因としてはこの実験では放射線を使用していないこと、また複雑な腫瘍免疫応答や各種炎症反応が複雑なことが原因と考える。しかしこの新機軸の治療法は他の癌腫での応用も可能であるため、今後さらなる研究の改良と継続が必要である。