Crosstalk between genomic abnormality and transcription activity for acquisition of stem cell property of cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19585
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Kanazawa University
• Principal Investigator: HIRAO Atsushi 金沢大学, がん進展制御研究所, 教授 (90343350)
• Research Collaborator: Kobayashi Masahiko
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 脳腫瘍 / 幹細胞

Outline of Final Research Achievements

In this study, we aimed to understand relationship between genomic abnormality and transcription activity for acquisition of stem cell property of brain tumor. We found that primary human astrocytes were immortalized by introducing gene mutations of 4 major tumor suppressors or oncogenes, however, they did not form remarkable tumor mass in vivo, unlike patient-derived glioma samples. In addition, introduction of 4 transcription factors which reportedly contribute to acquisition of stem cell property of differentiated glioma cells were not able to transform immortalized astrocytes into malignant status, indicating that additional mutations are required. In the paralleled experiments, we successfully generated a patient-derived glioma cell clone, in which GFP was inserted at the locus of a stem cell marker gene. Since this GFP system is useful for visualization of stemness of tumor, we expect that it contributes to discovery of factors essential for acquisition of cancer stemness.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により，がんの幹細胞特性の獲得には多くの因子の異常が複雑に関連していることが明らかとなった。また，本研究で得られた解析ツールを用いることにより，今後，未分化性獲得に必須のシグナルや治療標的を特定することにつながると期待された。本研究を通して得られた成果は，がんの診断，予防，治療の発展に寄与すると考えられ，将来，健康福祉の観点から社会に貢献することが期待される。