2006 Fiscal Year Final Research Report Summary
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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| 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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[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
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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
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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
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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
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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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