Analysis of molecular network on maintenance and differentiation of glioma stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25640068
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kumamoto University
• Principal Investigator: ARAKI Norie 熊本大学, その他の研究科, 准教授 (80253722)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: がん幹細胞 / プロテオミクス / 分子治療標的

Outline of Final Research Achievements

To identify the molecular network regulating the maintenance/differentiation of glioma stem cells (GSCs), we established 9 clones from patient’s gliomas having the potential to form glioblastomas, and subjected to iTRAQ, 2D-DIGE and DNA array based integrated proteomics. iPEACH analysis of 8,471 proteins and 21,857 mRNAs revealed that ECMs-integrins-RAS-MAPK/PI3K signalings were significantly upregulated during GSC differentiation. The differentiation was dramatically accelerated by the ligand ECMs, and suppressed by integrin inhibitors that raised GSC chemosensitivity. Combination of TMZ and their inhibitors suppressed glioma progression and led the longer survival of mouse xenograft models. These results demonstrate that GSCs induce ECMs/receptors-related network to regulate their stemness and differentiation process via developing specific niches. This is the first integrated proteomics providing new therapeutic ideas against the stem cell-associated malignant gliomas.

Free Research Field

腫瘍生化学