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Oct-3/4 promotes tumor angiogenesis through VEGF production in glioblastoma

Research Project

Project/Area Number 23592129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionEhime University

Principal Investigator

HISAAKI Takahashi  愛媛大学, 医学(系)研究科(研究院), 講師 (20363228)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords膠芽腫 / Oct-3/4 / 血管新生 / VEGF / HIF1 / AKT / グリオブラストーマ / 腫瘍幹細胞 / 浸潤
Research Abstract

Accumulating evidence shows that the expression level of Oct-3/4, a self-renewal regulator in stem cells, is positively correlated with the progression of various solid tumors. However, little is known regarding the influence of Oct-3/4 in the tumor angiogenesis of glioblastoma. In this study, we subcutaneously transplanted U251/EGFP-Oct-3/4 cells into nude mice to evaluate the roles of Oct-3/4 in the tumor angiogenesis. Both tumor size and the number of large vessels growing in the tumor were markedly increased. In an in vitro model of angiogenesis, conditioned media from U251/EGFP-Oct-3/4 cells significantly accelerated capillary-like tube formation. In U251/EGFP-Oct-3/4 cells, VEGF mRNA was upregulated under the control of HIF1a, and enhanced protein expression and nuclear translocation of HIF1a were observed. Our results demonstrate that Oct-3/4-expressing glioma cells have the ability to adapt to low-oxygen environments of tumor by promoting tumor angiogenesis.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (22 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (6 results) Remarks (4 results)

  • [Journal Article] Activated microglia in a rat stroke model express NG2 proteoglycan in peri-infarct tissue through the involvement of TGF-β12014

    • Author(s)
      Sugimoto K, Nishioka R, Ikeda A, Mise A, Takahashi H, Yano H, Kumon Y, Ohnishi T, Tanaka J
    • Journal Title

      GLIA

      Volume: 62 Pages: 185-198

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of MCP-1 and fractalkine on endothelial cells and astrocytes may contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions2013

    • Author(s)
      Tei N, Tanaka J, Sugimoto K, Nishihara T, Nishioka R, Takahashi H, Yano H, Matsumoto S, Ohue S, Watanabe H, Kumon Y, Ohnishi T
    • Journal Title

      J Neurosci Res

      Volume: 91 Pages: 681-693

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Postnatal interleukin-1βenhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats2013

    • Author(s)
      Fukuda M, Hino H, Suzuki Y, Takahashi H, Morimoto T, Ishii E
    • Journal Title

      Acta Neurologica Belgica

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of MCP-1 and fractalkine on endothelial cells and astrocytes may contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions2013

    • Author(s)
      Nari Tei
    • Journal Title

      J Neurosci Res

      Volume: 91 Issue: 5 Pages: 681693-681693

    • DOI

      10.1002/jnr.23202

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oct-3/4 promotes migration and invasion of glioblastoma cells2012

    • Author(s)
      Kobayashi K, Takahashi H, Inoue A, Harada H, Toshimori S, Kobayashi Y, Goto K, Sugimoto K, Yano H, Ohnishi T, Tanaka J
    • Journal Title

      J Cell Biochem

      Volume: 113(2) Pages: 508-517

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anticonvulsive effect of paeoniflorin on experimental febrile seizures in immature rats : possible application for febrile seizures in children2012

    • Author(s)
      Hino H, Takahashi H, Suzuki Y, Tanaka J, Ishii E, Fukuda M
    • Journal Title

      PLoS One

      Volume: 7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oct-3/4 promotes migration and invasion of glioblastoma cells2012

    • Author(s)
      Kobayashi K
    • Journal Title

      J Cell Biochem

      Volume: 113 Issue: 2 Pages: 508517-508517

    • DOI

      10.1002/jcb.23374

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anticonvulsive effect of paeoniflorin on experimental febrile seizures in immature rats: possible application for febrile seizures in children2012

    • Author(s)
      Hitomi Hino, Hisaaki Takahashi, Yuka Suzuki, Junya Tanaka, Eiichi Ishii, Mitsumasa Fukuda
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 8 Pages: e42920-e42920

    • DOI

      10.1371/journal.pone.0042920

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oct-3/4 promotes migration and invasion of glioblastoma cells.2012

    • Author(s)
      Kobayashi K, Takahashi H, Inoue A, Harada H, Toshimori S, Kobayashi Y, Goto K, Sugimoto K, Yano H, Ohnishi T, Tanaka J.
    • Journal Title

      J Cell Biochem.

      Volume: 113 (2) Pages: 508-517

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Subcutaneous injection containing IL-3 and GM-CSF ameliorates stab wound-induced brain injury in rats.2011

    • Author(s)
      Nishihara T, Ochi M, Sugimoto K, Takahashi H, Yano H, Kumon Y, Ohnishi T, Tanaka J.
    • Journal Title

      Exp Neurol.

      Volume: 229 (2) Pages: 507-516

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages.2011

    • Author(s)
      Nakata T, Kawachi K, Nagashima M, Yasugi T, Izutani H, Ryugo M, Okamura T, Shikata F, Imagawa H, Yano H, Takahashi H, Tanaka J.
    • Journal Title

      Brain Res.

      Volume: 1420 Pages: 114-124

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats.2011

    • Author(s)
      Choudhury ME, Sugimoto K, Kubo M, Nagai M, Nomoto M, Takahashi H, Yano H, Tanaka J.
    • Journal Title

      Brain Behav.

      Volume: 1 (1) Pages: 26-43

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Oct-3/4 promotes tumor angiogenesis in glioblastoma through VEGF production2014

    • Author(s)
      Takahashi H, Kawabe Y, Iwata S, Sugimoto K, Yano H, Tanaka J
    • Organizer
      日本生理学会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Final Research Report
  • [Presentation] Oct-3/4 promotes tumor angiogenesis in glioblastoma through VEGF production2014

    • Author(s)
      Hisaaki Takahashi, Yuya Kawabe, Shinji Iwata, Kana Sugimoto, Hajime Yano, Junya Tanaka
    • Organizer
      第91回日本生理学会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
  • [Presentation] Oct-3/4 induces CpG demethylation in MGMT promoter to acquire temozolomide resistance in glioblastoma cells2013

    • Author(s)
      Takahashi H, Inoue A, Kobayashi Y, Hosokawa Y, Harada H, Ohnishi T, Sugimoto K, Yano H, Tanaka J
    • Organizer
      日本生理学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Oct-3/4 induces CpG demethylation in the MGMT promoter to induce temozolomide resistance in glioblastoma cells2013

    • Author(s)
      Hisaaki Takahashi, Yukako Kobayashi, Kana Sugimoto, Hajime Yano, Junya Tanaka
    • Organizer
      第90回 日本生理学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Oct-3/4 promotes migration and invasion of glioblastoma cells2012

    • Author(s)
      Takahashi H, Kobayashi K, Inoue A, Harada H, Sugimoto K, Yano H, Ohnishi T, Tanaka J
    • Organizer
      日本生理学会
    • Place of Presentation
      松本
    • Related Report
      2013 Final Research Report
  • [Presentation] Oct-3/4 promotes migration and invasion of glioblastoma cells2012

    • Author(s)
      Hisaaki Takahashi, Kana Kobayashi, Akihiro Inoue, Hironobu Harada, Kana Sugimoto, Hajime Yano, Takanori Ohnishi, Junya Tanaka
    • Organizer
      第89回 日本生理学会大会
    • Place of Presentation
      長野・松本
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://hgyano.jimdo.com/

    • Related Report
      2013 Final Research Report
  • [Remarks] 愛媛大学大学院医学系研究科分子細胞生理学研究室ホームページ

    • URL

      http://hgyano.jimdo.com/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 愛媛大学大学院医学系研究科分子細胞生理学 研究紹介

    • URL

      http://www.m.ehime-u.ac.jp/school/kisogp/contents/laboratories

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.proteo.ehime-u.ac.jp/section/06.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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