System development for microquantitative molecular analyses ofglioma stem cells
| 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 |
|---|
| 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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Report
(3 results)
Research Products
(87 results)
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[Journal Article] Gliomainitiating cells form a differentiation nichevia the induction of extracellular matrices andintegrin alpha V2013
Author(s)
Nambu, NA., Midorikawa U, Mizuguchi S,Hide T, Nagai M, Komohara Y, Nagayama1M, Hirayama M, Kobayashi D, Tsubota N,Takezaki T, Makino K, Nakamura H, TakeyaM, Kuratsu J and Araki N
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Enhancement of human cancer cell motilityand invasiveness by anaphylatoxin C5a viaaberrantly expressed C5a-receptor (CD88)2013
Author(s)
Nitta H, Wada Y, Kawano Y, Murakami Y,Irie A, Taniguchi K, Kikuchi K, Yamada G、Suzuki K, Honda J, Wilson MM, Araki N,Eto M, Baba H and Imamura T
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Journal Title
Clinical Cancer Research
Volume: 19(8)
Pages: 1-10
Related Report
Peer Reviewed
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[Journal Article] Integrated view of the human chromosome X-centric proteome project.2013
Author(s)
Yamamoto T, Nakayama K, Hirano H, Tomonaga T, Ishihama Y, Yamada T, Kondo T,Kodera Y, Sato Y, Araki N, Mamitsuka H, Goshima N.
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Journal Title
J Proteome Res.
Volume: 12
Issue: 1
Pages: 58-61
DOI
Related Report
Peer Reviewed
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[Journal Article] Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrin alpha V.2013
Author(s)
Nambu, NA., Midorikawa U, Mizuguchi S, Hide T, Nagai M, Komohara Y, Nagayama1 M, Hirayama M, Kobayashi D, Tsubota N, Takezaki T, Makino K, Nakamura H, Takeya M, Kuratsu J and Araki N*.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a-receptor (CD88).2013
Author(s)
Nitta H, Wada Y, Kawano Y, Murakami Y, Irie A, Taniguchi K, Kikuchi K, Yamada G, Suzuki K, Honda J, Wilson MM, Araki N, Eto M, Baba H and Imamura T.
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Journal Title
Clinical Cancer Research
Volume: 19(8)
Pages: 1-10
Related Report
Peer Reviewed
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[Presentation] An integrated proteomics by iPEACH, anew application, identified novel activatedsignal cascades in chemotherapy resistantmalignant gliomas2012
Author(s)
Araki N, Mizugushi S, Morikawa T ,kawano S, Y amaguchi A, Kobayashi D,Hirayama M, Midorikawa U, Nakamura H,Kuratsu J. HUPO
Organizer
11th Annual WorldCongress
Place of Presentation
Hynes Convention Center, Boston,US
Related Report
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[Presentation] Integrated Proteomics Identified Translationally Controlled Tumor Proteinas a Biological Target for Neurofibroma andMalignant Peripheral Nerve Sheath Tumors2012
Author(s)
Kobayashi D, Hirayama M, Komohara Y ,Mizuguchi S, Wilson-morifuji M, Ihn h,Takeya M, Kuramochi A, Araki N
Organizer
11th Annual World Congress
Place of Presentation
Hynes Convention Center, Boston,US
Related Report
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[Presentation] An integrated proteomics by iPEACH, a new application, identified novel activated signal cascades in chemotherapy resistant malignant gliomas2012
Author(s)
Araki N, Mizugushi S, Morikawa T, kawano S, Yamaguchi A, Kobayashi D, Hirayama M, Midorikawa U, Nakamura H, Kuratsu J
Organizer
HUPO 11th Annual World Congress
Place of Presentation
Hynes Convention Center,Boston,US
Related Report
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[Presentation] Integrated Proteomics Identified Translationally Controlled Tumor Protein as a Biological Target for Neurofibroma and Malignant Peripheral Nerve Sheath Tumors2012
Author(s)
Kobayashi D, Hirayama M, Komohara Y, Mizuguchi S, Wilson-morifuji M, Ihn h, Takeya M, Kuramochi A, Araki N.
Organizer
HUPO 11th Annual World Congress
Place of Presentation
Hynes Convention Center,Boston,US
Related Report
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