Analysis of Invasion niche and exploration of cancer stem cell

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08997
• 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: Ehime University
• Principal Investigator: Akihiro Inoue 愛媛大学, 医学部附属病院, 講師 (20593403)
• Co-Investigator(Kenkyū-buntansha): 西川 真弘 愛媛大学, 医学部附属病院, 助教 (20794308) ; 國枝 武治 愛媛大学, 医学系研究科, 教授 (60609931)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 腫瘍幹細胞 / Glioblastoma / CD44 / High invasive type

Outline of Final Research Achievements

We showed that GSCs that express high levels of CD44 are present in the tumor periphery. We also found that vascular endothelial growth factor (VEGF) is characteristically expressed at a high level in the tumor periphery. Cultured GSCs obtained from the tumor periphery were highly invasive and have enhanced migration phenotype, both of which were markedly inhibited by CD44 knockdown. Higher expression of CD44 in the tumor periphery than in the core was correlated with a highly invasive feature on MRI and was associated with early tumor progression and worse survival, whereas lower expression of CD44 in the tumor periphery corresponded to low invasion and was associated with longer survival. The low invasion type on MRI tended to show high levels of VEGF expression in the tumor periphery, thus presenting the tumor with high proliferative activity.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

CSCは発癌における責任細胞であり、ニッチを形成する微小環境と腫瘍幹細胞性獲得との関係などを個体レベルで解明していくことは、臨床的にも腫瘍細胞生物学的にも大きな発展が期待できる。さらに本研究の最大の独自的な特色は「 Invasion niche に潜む CSC が神経膠腫浸潤の主因である」という仮定に基づき、in vivo 光イメージングシステムや小動物用 MRIを用い、細胞浸潤を時空間的に腫瘍組織全体で解明しようとしている点にある。将来的には血管新生阻害剤や他の新規分子標的薬とCSCの幹細胞性破綻とを組み合わせた新しい神経膠腫治療の開発に繋げることも可能であり、社会的意義は絶大である。