| Project/Area Number |
25640068
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Kumamoto University |
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Principal Investigator |
ARAKI Norie 熊本大学, その他の研究科, 准教授 (80253722)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | がん幹細胞 / プロテオミクス / 分子治療標的 / グリオーマ幹細胞 / 融合プロテオミクス / mTOR / 幹細胞 |
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| 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.
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