| Project/Area Number |
23659693
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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 |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
ARAKI Norie 熊本大学, 大学院・生命科学研究部, 准教授 (80253722)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | がん幹細胞 / グリオーマ幹細胞 / 融合プロテオミクス / ニッチ / インテグリン / 細胞外マトリクス / プロテオミクス / トランスクリプトーム / プロテオ-ム |
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| Research Abstract |
Glioma initiating cells (GICs) are considered responsible for thetherapeutic resistance and recurrence of malignant glioma. T o clarify the molecularmechanism of GIC differentiation, we established GIC clones which differentiate intomalignant gliomas, and subjected to DNA microarray/iTRAQ based integrated proteomics(iPEACH). GO analysis revealed that the expression of cell adhesion molecules, includingintegrin subfamilies and ECMs, was significantly upregulated during serum-induced GICdifferentiation. This process, also accompanied by the upregulation of MAPK/PI3K signals,was dramatically accelerated by these ECMs and suppressed by integrin inhibitors such asRGD which also inhibited GIC proliferation, and raised their sensitivity against TMZ.Combination treatments of TMZ and RGD inhibit glioma progression and lead the longersurvival of mouse intracranial GIC xenograft model. GICs induce/secrete ECMs to developmicroenvironments, namely differentiation niches that further stimulate GICdifferentiation and proliferation via the integrin recognition motif RGD. This studyprovides a new perspective for developing therapeutic strategies against the early onset ofGIC-associated glioma.
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