The identification of invasion associated genes in glioma stem cell

• Project/Area Number: 21689038
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Kanazawa University
• Principal Investigator: NAKADA Mitsutoshi Kanazawa University, 医学系, 助教 (20334774)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2009: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
• Keywords: グリオーマ / 幹細胞 / 浸潤 / インテグリン

Research Abstract

Glioma stem-like cells are shown to be invasive but its mechanism remains to be elucidated. In this study we demonstrate the function of integrin in glioma stem-like cell invasion. The expression profile of integrin family in CD133+ and - cells was determined. Integrin α3 was overexpressed in CD133+ cells compared with CD133- cells. Immunohistochemistry demonstrated the localization of integrin alpha3 in invading glioblastoma cells. The activity of glioma cell invasion was associated with the expression level of integrin α3. The migration activity of glioma cell lines was linked to the phosphorylation level of ERK (extracellular signal-regulated kinase) 1/2. Our results suggest that endogenous integrin alpha3 contributes the invasive nature of glioma stem-like cells, which renders integrin alpha3 as a prime candidate for anti-invasion therapy for glioblastoma.

Research Products

• [Journal Article] MGMT promoter methylation and temozolomide response in choroid plexus carcinoma. (2011)
  • Author(s): Misaki K, Nakada M, Mohri M, Hayashi Y, Hamada JI.
  • Journal Title: Brain Tumor Pathol (Epub ahead of print)
  • NAID: 120003479726
  • Peer Reviewed
• [Journal Article] Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy. (2011)
  • Author(s): Teng L, Nakada M, Zhao SG, Endo Y, Furuyama N, Nambu E, Pyko IV, Hayashi Y, Hamada JI.
  • Journal Title: British Journal of Cancer 104 Pages: 798-807
  • Peer Reviewed
• [Journal Article] Epithelioid glioblastoma changed to typical glioblastoma : the methylation status of MGMT promoter and 5-ALA fluorescence. (2011)
  • Author(s): Tanaka S, Nakada M, Hayashi Y, Nakada S, Kitamura-Sawada S, Furuyama N, Suzuki T, Kamide T, Hayashi Y, Yano S, Hamada JI.
  • Journal Title: Brain Tumor Pathol 28 Pages: 59-64
  • Peer Reviewed
• [Journal Article] NKX2.2 suppresses self-renewal of glioma-initiating cells. (2011)
  • Author(s): Muraguchi T, Tanaka S, Yamada D, Tamase A, Nakada M, Nakamura H, Hoshii T, Ooshio T, Tadokoro Y, Naka K, Ino Y, Todo T, Kuratsu JI, Saya H, Hamada JI, Hirao A.
  • Journal Title: Can Res 71 Pages: 1135-1145
  • Peer Reviewed
• [Journal Article] The correlation between promoter methylation status and the expression level of O6-methylguanine-DNA methyltransferase in recurrent glioma. (2011)
  • Author(s): Suzuki T, Nakada M, Yoshida Y, Nambu E, Furuyama N, Kita D, Hayashi Y, Hayashi Y, Hamada JI.
  • Journal Title: Jpn J Clin Oncol 41 Pages: 190-196
  • Peer Reviewed
• [Journal Article] Target signaling pathways in glioma. (2011)
  • Author(s): Nakada M
  • Journal Title: Cancers Volume: (in press)
  • Peer Reviewed
• [Journal Article] MGMT promoter methylation and temozolomide response in choroid plexus carcinoma : a case report and literature review (2011)
  • Author(s): Misaki K
  • Journal Title: Brain Tumor Pathol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy (2011)
  • Author(s): Teng L
  • Journal Title: British Journal of Cancer Volume: 104 Pages: 798-807
  • Peer Reviewed
• [Journal Article] Anaplastic meningioma with extremely rapid recurrence (2011)
  • Author(s): Kawahara Y
  • Journal Title: Neurol Med Chir (Tokyo) Volume: (in press)
  • Peer Reviewed
• [Journal Article] Epithelioid glioblastoma changed to typical glioblastoma : the methylation status of MGMT promoter and 5-ALA fluorescence (2011)
  • Author(s): Tanaka S
  • Journal Title: Brain Tumor Pathol Volume: 28 Pages: 59-64
  • Peer Reviewed
• [Journal Article] The correlation between promoter methylation status and the expression level of O^6-methylguanine-DNA methyltransferase in recurrent glioma (2011)
  • Author(s): Suzuki T
  • Journal Title: Jpn J Clin Oncol Volume: 41 Pages: 190-196
  • Peer Reviewed
• [Journal Article] PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas (2011)
  • Author(s): Ozawa T
  • Journal Title: Genes & Development Volume: 24 Pages: 2205-2218
  • Peer Reviewed
• [Journal Article] Secondary anaplastic astrocytoma developing in a young adult with autoimmune lymphoproliferative syndrome (ALPS). (2010)
  • Author(s): Kita D, Hayashi Y, Watanabe T, Korshunov A, von Deimling A, Nakada M, Kinoshita M, Uchiyama N, Kasahara Y, Zen Y, Hamada JI, Hayashi Y.
  • Journal Title: Neuropathology and Applied Neurobiology (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. (2010)
  • Author(s): Ozawa T, Brennan CW, Wang L, Squatrito M, Sasayama T, Nakada M, Huse JT, Pedraza A, Utsuki S, Yasui Y, Tandon A, Fomchenko EI, Oka H, Levine RL, Fujii K, Ladanyi M, Holland EC.
  • Journal Title: Genes & Development 24 Pages: 2205-2218
  • Peer Reviewed
• [Journal Article] The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients. (2010)
  • Author(s): Yoshida Y, Nakada M, Harada T, Tanaka S, Furuta T, Hayashi Y, Kita D, Uchiyama N, Hayashi Y, Hamada JI.
  • Journal Title: J Neurooncol 98 Pages: 41-47
  • Peer Reviewed
• [Journal Article] The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion. (2010)
  • Author(s): Nakada M, Anderson EM, Demuth T, Nakada S, Reavie LB, Drake KL, Hoelzinger DB, Berens ME.
  • Journal Title: Int J Cancer 126 Pages: 1155-1165
  • Peer Reviewed
• [Journal Article] Sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with survival of patients with glioblastoma. (2010)
  • Author(s): Yoshida Y, Nakada M, Sugimoto N, Harada T, Hayashi Y, Kita D, Uchiyama N, Hayashi Y, Yachie A, Takuwa Y, Hamada JI.
  • Journal Title: Int J Cancer 126 Pages: 2341-2352
  • Peer Reviewed
• [Journal Article] Radiation induced cerebellar high grade glioma accompanied by meningioma and cavernoma 29 years after the treatment of medulloblastoma : a case report. (2010)
  • Author(s): Kamide T, Nakada M, Hayashi Y, Suzuki T, Hayashi Y, Uchiyama N, Kijima T, Hamada JI.
  • Journal Title: J Neurooncol 100 Pages: 299-303
  • Peer Reviewed
• [Journal Article] NKX2.2 suppresses self-renewal of glioma-initiating cells (2010)
  • Author(s): Muraguchi T
  • Journal Title: Can Res Volume: 71 Pages: 1135-1145
  • Peer Reviewed
• [Journal Article] Secondary anaplastic astrocytoma developing in a young adult with autoimmune lymphoproliferative syndrome (ALPS) (2010)
  • Author(s): Kita D
  • Journal Title: Neuropathology and Applied Neurobiology Volume: Sep 15
  • Peer Reviewed
• [Journal Article] The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients (2010)
  • Author(s): Yoshida Y
  • Journal Title: J Neurooncol Volume: 98 Pages: 41-47
  • Peer Reviewed
• [Journal Article] The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion (2010)
  • Author(s): Nakada M
  • Journal Title: Int J Cancer 126 Pages: 1155-1165
  • Peer Reviewed
• [Journal Article] Sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with survival of patients with glioblastoma (2010)
  • Author(s): Yoshida Y
  • Journal Title: Int J Cancer 126 Pages: 2341-2352
  • Peer Reviewed
• [Journal Article] Radiation induced cerebellar high grade glioma accompanied with meningioma and cavernoma 29 years after the treatment of medulloblastoma (2010)
  • Author(s): Kamide T
  • Journal Title: J Neurooncol (in press)
  • Peer Reviewed
• [Journal Article] Implication of 5-ALA fluorescence of the ventricle wall for postoperative communicating hydrocephalus associated with CSF dissemination in glioblastoma patients - A report of seven cases - (2010)
  • Author(s): Hayashi Y
  • Journal Title: Journal of Neurosurgery (in press)
  • Peer Reviewed
• [Journal Article] Potential effect of glycogen synthase kinase 3β inhibition against human glioblastoma. (2009)
  • Author(s): Miyashita K, Kawakami K, Nakada M, Mai W, Shakoori A, Fujisawa H, Hayashi Y, Hamada JI, Minamoto T.
  • Journal Title: Clin Can Res 15 Pages: 887-897
  • Peer Reviewed
• [Journal Article] Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin. (2009)
  • Author(s): Tamase A, Muraguchi T, Naka K, Tanaka S, Kinoshita M, Hoshii T, Ohmura M, Shugo H, Ooshio T, Nakada M, Sawamoto K, Onodera M, Matsumoto K, Oshima M, Asano M, Saya H, Okano H, Suda T, Hamada JI, Hirao A.
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 17163-17168
  • Peer Reviewed
• [Journal Article] An emerging strategy for cancer treatment targeting aberrant glycogen synthase kinase 3β. (2009)
  • Author(s): Miyashita K, Nakada M, Shakoori A, Ishigaki Y, Shimasaki T, Motoo Y, Kawakami K, Minamoto T.
  • Journal Title: Anti-Cancer Agents in Medicinal Chemistry 9 Pages: 1114-1122
  • NAID: 120001856980
• [Journal Article] Potential effect of glycogen synthase kinase 3β inhibition against human glioblastoma (2009)
  • Author(s): Miyashita K
  • Journal Title: Clin Can Res 15 Pages: 887-897
  • Peer Reviewed
• [Journal Article] Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin (2009)
  • Author(s): Tamase A
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 17163-17168
  • Peer Reviewed
• [Journal Article] An emerging strategy for cancer treatment targeting aberrant glycogen synthase kinase 3β (2009)
  • Author(s): Miyashita K
  • Journal Title: Anti-Cancer Agents in Medicinal Chemistry 9 Pages: 1114-1122
  • Peer Reviewed
• [Journal Article] BCL10 single nucleotide polymorphism and its association with CSF dissemination of primary intracranial germ cell tumors (2009)
  • Author(s): Hayashi Y
  • Journal Title: Pediatr Neurosurg 45 Pages: 291-295
  • Peer Reviewed
• [Journal Article] Target signaling pathways in glioma.
  • Author(s): Nakada M, Kita D, Watanabe T, Hayashi Y, Teng L, Pyko IV, Hamada JI.
  • Journal Title: Cancers in press
  • Peer Reviewed
• [Presentation] 既存の薬剤を使用した悪性脳腫瘍に対する分子標的療法(講演) (2010)
  • Author(s): 中田光俊
  • Organizer: 創剤フォーラム第16回シンポジウム
  • Place of Presentation: アルカディア市ヶ谷(東京都)(講演)
  • Year and Date: 2010-10-22
• [Presentation] 既存め薬剤を使用した悪性脳腫瘍に対する分子標的療法 (2010)
  • Author(s): 中田光俊
  • Organizer: 創剤フォーラム第16回シンポジウム
  • Place of Presentation: アルカディア市ヶ谷(東京都)(招待講演)
  • Year and Date: 2010-10-22
• [Presentation] 悪性脳腫瘍の浸潤機構と化学療法 (2010)
  • Author(s): 中田光俊
  • Organizer: Global COE "NetworkMedicine"主催セミナー
  • Place of Presentation: 東北大学(宮城県)(講演)
  • Year and Date: 2010-07-20
• [Presentation] 悪性脳腫瘍の浸潤機構と化学療法 (2010)
  • Author(s): 中田光俊
  • Organizer: Global COE"Network Medicine"主催セミナー
  • Place of Presentation: 東北大学(宮城県)(招待講演)
  • Year and Date: 2010-07-20
• [Presentation] 悪性グリオーマの浸潤機構と抗浸潤療法 (2010)
  • Author(s): 中田光俊
  • Organizer: 第5回脳腫瘍の基礎シンポジウム
  • Place of Presentation: 大手町サンケイプラザ(東京都)(特別講演)
  • Year and Date: 2010-01-30
• [Presentation] 悪性グリオーマ治療における最近の進歩と我々の試み (2010)
  • Author(s): 中田光俊
  • Organizer: 第5回脳腫瘍の基礎シンポジウム
  • Place of Presentation: 大手町サンケイプラザ(東京都)
  • Year and Date: 2010-01-30
• [Presentation] Integrin alpha3 is involved in the invasive behavior of glioma stem-like cells. (2010)
  • Author(s): Nakada M, Nambu E, Furuyama N, Yoshida Y, Kita D, Hayashi Y, Hayashi Y, Hamada JI.
  • Organizer: Society for Neuro-Onology 15th Annual Meeting 2010
  • Place of Presentation: Le Centre Sheraton Hotel (Canada)
• [Presentation] 膠芽腫におけるGSK3β研究の進展とその阻害薬剤を使用した再発膠芽腫に対する第I/II相臨床試験 (2010)
  • Author(s): 中田光俊、林裕、宮下勝吉、渡邉卓也、Pyko Ilya、喜多大輔、近野祐里、林康彦、内山尚之、川上和之、源利成、濱田潤一郎
  • Organizer: 第69 回日本脳神経外科学会総会
  • Place of Presentation: 福岡コンベンションセンター(福岡県)
• [Presentation] Clinical trial for treatment of recurrent glioblastoma targeting deregulated GSK3β in combination with temozolomide (2010)
  • Author(s): 中田光俊、林裕、宮下勝吉、喜多大輔、林康彦、内山尚之、川上和之、源利成、濱田潤一郎
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
• [Presentation] 定量的プロテオミクスを利用した悪性脳腫瘍に対する個別化分子標的療法 (2010)
  • Author(s): 中田光俊、林裕、渡邉卓也、吉川陽文、長谷川貴之、河原庸介、池田千絵美、大槻純男、寺崎哲也、濱田潤一郎
  • Organizer: 第11回日本分子脳神経外科学会
  • Place of Presentation: 艮陵会館記念ホール(宮城県)
• [Presentation] The mechanism of glioma invasion and anti-invasion therapy. (2010)
  • Author(s): Nakada M.
  • Organizer: The 4^<th> Harbin International Neurosurgical Conference.
  • Place of Presentation: Harbin Medical University (中国)(Invited Lecture)
• [Presentation] Eph/ephrin tyrosine kinase in glioma invasion. (2010)
  • Author(s): Nakada M.
  • Organizer: 7^<th> Meeting for the Asian Society for Neuro-Oncology
  • Place of Presentation: JW Marriott Hotel (韓国)(Meet the Expert Lecture)
• [Presentation] Targeting glycogen synthase kinase 3β in adult recurrent glioblastomas. (2010)
  • Author(s): Nakada M, Hayashi Y, Miyashita K, Kita D, Hayashi Y, Uchiyama N, Kawakami K, Minamoto T, Hamada JI.
  • Organizer: 7^<th> Meeting for the Asian Society for Neuro-Oncology
  • Place of Presentation: JW Marriott Hotel (韓国)(Oral presentation)
• [Presentation] 再発膠芽腫に対するGSK3β阻害薬剤を使用した第I/II相臨床試験 (2010)
  • Author(s): 中田光俊
  • Organizer: 第28回日本脳腫瘍学会
  • Place of Presentation: 軽井沢プリンスホテル(長野県)
• [Presentation] Integrin alpha3 is involved in the invasive behavior of glioma stem-like cells (2010)
  • Author(s): Nakada M
  • Organizer: Society for Neuro-Onology 15th Annual Meeting 2010
  • Place of Presentation: Le Centre Sheraton Hotel(カナダ・モントリオール)
• [Presentation] 膠芽腫におけるGSK3β研究め進展とその阻害薬剤を使用した再発膠芽腫に対する第I/II相臨床試験 (2010)
  • Author(s): 中田光俊
  • Organizer: 第69回日本脳神経外科学会総会
  • Place of Presentation: 福岡コンベンションセンター(福岡県)
• [Presentation] The mechanism of glioma invasion and anti-invasion therapy. (2010)
  • Author(s): Nakada M
  • Organizer: The 4^<th> Harbin International Neurosurgical Conference
  • Place of Presentation: Harbin Medical University(中国・ハルビン)(招待講演)
• [Presentation] Eph/ephrin tyrosine kinase in glioma invasion. (2010)
  • Author(s): Nakada M
  • Organizer: 7^<th> Meeting for the Asian Society for Neuro-Oncology
  • Place of Presentation: JW Marriott Hotel(韓国・ソウル)(招待講演)
• [Presentation] Targeting glycogen synthase kinase 3β in adult recurrent glioblastomas. (2010)
  • Author(s): Nakada M
  • Organizer: 7^<th> Meeting for the Asian Society for Neuro-Oncology
  • Place of Presentation: JW Marriott Hotel(韓国・ソウル)
• [Presentation] Ephrin-A2 modulates glioma cell invasion via EphA2 signaling and correlates with patients survival in glioblastomas. (2010)
  • Author(s): Nakada M
  • Organizer: The 18^<th> International Conference on Brain Tumor Research & Therapy
  • Place of Presentation: Grand Spa Resort Arosa(ドイツ・トラフェミュンデ)
• [Presentation] Integrin alpha3 prevents neurosphere formation and proliferation of glioma stem cells. (2009)
  • Author(s): Nakada M, Nambu E, Yoshida Y, Furuyama N, Kita D, Hayashi Y, Hayashi Y, Uchiyama N, Hamada JI.
  • Organizer: 2009 Joint Meeting of the Society for Neuro-Oncology and the AAAS/CNS Section on Tumors
  • Place of Presentation: Hilton New Orleans Riverside (USA)
• [Presentation] 再発神経膠芽腫に対するGSK3βを分子標的としたPhaseI/II相臨床試験(シンポジウム) (2009)
  • Author(s): 中田光俊、林裕、喜多大輔、宮下勝吉、玉瀬玲、上出智也、田中慎吾、林康彦、内山尚之、源利成、濱田潤一郎
  • Organizer: 第68回日本脳神経外科学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] 5-ALA内服後血中プロトポルフィリンIX計測による腫瘍再発と放射線壊死の鑑別 (2009)
  • Author(s): 中田光俊
  • Organizer: 第27回日本脳腫瘍学会
  • Place of Presentation: りんくう国際会議場(大阪府)
• [Presentation] Integrin alpha3 prevents neurosphere formation and proliferation of glioma stem cells (2009)
  • Author(s): Nakada M
  • Organizer: 2009 Joint Meeting of the Society for Neuro-Oncology and the AAAS/CNS Section on Tumors
  • Place of Presentation: Hilton New Orleans Riverside(USA)
• [Presentation] 再発神経膠芽腫に対するGSK3βを分子標的としたPhase I/II臨床試験 (2009)
  • Author(s): 中田光俊
  • Organizer: 第68回日本脳神経外科学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
• [Presentation] Ephrin-A2 regulates glioma cell invasion through EphA signaling and predicts patient survival (2009)
  • Author(s): 中田光俊
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Book] Brain Tumor Book 2(The pivotal role of GSK3β in glioma biology.)(ed.Miklos Garami) (2011)
  • Author(s): Nakada M, Minamoto T, Pyko IV, Hayashi Y, Hamada JI.
  • Publisher: InTech in press
• [Book] Brain Tumor/Book 2, ed.Miklos Garami, InTech (2011)
  • Author(s): Nakada M
  • Publisher: The pivotal role of GSK3β in glioma biology.(In press)
• [Book] RNA Technologies and Their Applications(RNAi in malignant brain tumors : relevance to molecular and translational research.)eds.Erdmann VA & Barciszewski J) (2010)
  • Author(s): Nakada M, Kita D, Hayashi Y, Kawakami K, Hamada JI, Minamoto T.
  • Publisher: Springer-Verlag Heidelberg
• [Book] RNA Technologies and Their Applications (2010)
  • Author(s): Nakada M
  • Publisher: Springer-Verlag
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~med28/index.htm
• [Patent(Industrial Property Rights)] 脳腫瘍治療用キット及び脳腫瘍治療方法 (2010)
  • Inventor(s): 中田光俊、源利成、林裕、濱田潤一郎
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 2010-018569
  • Filing Date: 2010-08-22
• [Patent(Industrial Property Rights)] 脳腫瘍治療用キット及び脳腫瘍治療方法 (2010)
  • Inventor(s): 中田光俊
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 2010-018569
  • Filing Date: 2010-08-22