Development of novel mouse brain tumor model using in vivo electroporation and piggyBac system

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07125
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Keio University
• Principal Investigator: Onishi Nobuyuki 慶應義塾大学, 医学部(信濃町), 訪問研究員 (40534540)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: マウス脳腫瘍モデル / In vivoエレクトロポレーション / piggyBacシステム / 神経幹細胞

Outline of Final Research Achievements

Glioblastoma multiforme (GBM), is one of the most malignant brain tumors, has highly-proliferative and invasive characters. To understand these malignant characters of GBM, an appropriate carcinogenesis model is required. Loss of INK4A/ARF and stimulation of common signal transduction pathways involving RAS are frequently found in GBM. Previously, we have established a stable mouse models of brain tumors, transplanting the genetically modified neural stem cells (NSCs). Recently, for the purpose of reproducing a clinical tumor initiating process, we are developing a novel mouse model of brain tumors by gene transfer into mouse brain directly. Using in vivo electroporation and piggyBac system, transduction of activated-H-RAS and shInk4a/Arf into NSCs in mouse brain, efficiently formed highly proliferative, invasive and heterogeneous brain tumors. Based on these findings, we propose this in vivo carcinogenesis technique is efficient method to generate appropriate mouse brain tumor models.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

悪性脳腫瘍、特にグリオブラストーマ(glioblastoma multiforme: GBM)は原発性脳腫瘍のうち悪性度が最も高く、浸潤の早さから手術による全摘は困難とされており、平均生存期間は約1年と極めて予後不良な悪性腫瘍である。GBMは放射線・化学療法に抵抗性を持ち、効果的な治療は未だ確立されていない。GBMの性状を理解し、新たな治療戦略を考案するためには適切な発がんモデルの構築が必須である。本研究で構築したマウス脳腫瘍モデルは、ヒトGBMに酷似した特徴を有する脳腫瘍を簡便な方法で作製することができ、最も予後が悪く難治性のがんの一つであるGBMの治療を目指した研究を促進するものである。