Analysis of the mechanism of invasive growth of human glioblastomas. PART II
| Project/Area Number |
17390391
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Gunma University |
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Principal Investigator |
ISHIUCHI Shogo Gunma University, School of Medicine, assistant Professor (10312878)
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| Co-Investigator(Kenkyū-buntansha) |
OZAWA Seiji Gunma University, 理事 (40049044)
SAITO Nobuhito The University of Tokyo, Hospital, Professor (60262002)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,900,000 (Direct Cost: ¥15,900,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥14,200,000 (Direct Cost: ¥14,200,000)
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| Keywords | glioblastoma / invasive growth / signal transduction / glutamate / AMPA antagonists |
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| Research Abstract |
Evidence has accumulated that glioblastoma cells release and exploit glutamate for proliferation and migration by autocrine or paracrine loops.
Ca^<2+>-permeable-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors are important role for the invasive growth of human glioblastomas. Here we show that Ca^<2+> signaling mediated by AMPA receptors regulates the growth and motility of glioblastoma cells via activation of Akt. Ca^<2+> supplied through Ca^<2+>-permeable AMPA receptors phosphorylated Akt at Ser-473, thereby facilitating proliferation and mobility. A dominant negative form of Akt inhibited proliferation and migration accelerated by overexpression of Ca^<2+>-permeable AMPA receptors. In contrast, introduction of a constitutively active form of Akt rescued tumor cells from apoptosis induced by the conversion of Ca^<2+>-permeable AMPA receptors to Ca^<2+>-impermeable receptors by the delivery of GluR2 cDNA.
Therefore, Akt functions as a downstream effector for Ca^<2+>-signaling mediated by AMPA receptors in glioblastoma cells. Glutamate released by glioma cells is involved in Akt activity through Ca^<2+>-permeable AMPA receptors and the activation of Glutamate-AMPA-Akt pathway contributes to the high degree of anaplasia and invasive growth of human glioblastoma. Thus this novel pathway might give alternative therapeutic target.
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Report
(3 results)
Research Products
(31 results)
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[Journal Article] Cat+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation2007
Author(s)
Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T, Saito N, Tsuzuki K, Okado H, Miwa A, Nakazato Y, Ozawa S.
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Journal Title
J Neurosci. 27
Pages: 7987-8001
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation.2007
Author(s)
Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T, Saito N, Tsuzuki K, Okado H, Miwa A, Nakazato Y, Ozawa S.
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Journal Title
J Neurosci. 27
Pages: 7987-8001
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] MR signal of the solid portion of pilocytic astrocytoma on T2-weighted images:is it useful for differentiation from medulloblastoma2006
Author(s)
Arai K, Sato N, Aoki J, Yagi A, Taketomi-Takashi A, Morita H, Koyama Y, Oba H, Ishiuchi S, Saito N, Endo K.
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Journal Title
Neuroradiology 48
Pages: 233-237
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] MR signal of the solid portion of pilocytic astrocytoma on T2-weighted images : is it useful for differentiation from medulloblastoma?2006
Author(s)
Arai K, Sato N, Aoki J, Yagi A, Taketomi-Takahashi A, Morita H, Koyama Y, Oba H, Ishiuchi S, Saito N, Endo K.
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Journal Title
Neuroradiology. 48
Pages: 233-7
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] RBE values of Heavy Ion Beams and Therapeutic Ratios2006
Author(s)
Hasegawa M, Ishiuchi S, Sakurai H, Nakano T, Suzuki Y, Takeuchi A, Asakawa I, Tamamoto T, Ono T, Ishikawa H, Kato S, Nojima K.
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Journal Title
Natl Inst Radiol Sci 192
Pages: 69-70
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 浸潤性増殖を示す神経膠芽腫に対する重イオンマイクロビーム照射の増殖抑制効果2005
Author(s)
Y石内勝吾, 長谷川正俊, 中野隆史, 桜井英幸, 斉藤延人, 中里洋一, 小澤瀞司, 舟山知夫, 小林泰彦, 坂下哲也, 和田成一, 浜田信行
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Journal Title
第14回TIARA研究発表会要旨集
Pages: 117-117
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[Journal Article] MR signals of solid portion of pilocytic astrocytoma on T2-weighted imaging : Is it useful for differentiation from medulloblastoma?
Author(s)
Arai K, Sato N, Aoki J, Yagi A, Taketomi A, Morita H, Koyama Y, Obata H, Ishiuchi S, Saito N, Endo K.
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Journal Title
Neuroradiology (in press)
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