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

• Project/Area Number: 23592129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Ehime 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: ¥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.

Research Products

• [Journal Article] Activated microglia in a rat stroke model express NG2 proteoglycan in peri-infarct tissue through the involvement of TGF-β1 (2014)
  • 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
  • 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 lesions (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Postnatal interleukin-1βenhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats (2013)
  • Author(s): Fukuda M, Hino H, Suzuki Y, Takahashi H, Morimoto T, Ishii E
  • Journal Title: Acta Neurologica Belgica Volume: (in press)
  • 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 lesions (2013)
  • Author(s): Nari Tei
  • Journal Title: J Neurosci Res Volume: 91 Issue: 5 Pages: 681693-681693
  • DOI: 10.1002/jnr.23202
  • 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
  • Peer Reviewed
• [Journal Article] Anticonvulsive effect of paeoniflorin on experimental febrile seizures in immature rats : possible application for febrile seizures in children (2012)
  • Author(s): Hino H, Takahashi H, Suzuki Y, Tanaka J, Ishii E, Fukuda M
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Oct-3/4 promotes migration and invasion of glioblastoma cells (2012)
  • Author(s): Kobayashi K
  • Journal Title: J Cell Biochem Volume: 113 Issue: 2 Pages: 508517-508517
  • DOI: 10.1002/jcb.23374
  • Peer Reviewed
• [Journal Article] Anticonvulsive effect of paeoniflorin on experimental febrile seizures in immature rats: possible application for febrile seizures in children (2012)
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Oct-3/4 promotes tumor angiogenesis in glioblastoma through VEGF production (2014)
  • 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
• [Presentation] Oct-3/4 promotes tumor angiogenesis in glioblastoma through VEGF production (2014)
  • 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
• [Presentation] Oct-3/4 induces CpG demethylation in MGMT promoter to acquire temozolomide resistance in glioblastoma cells (2013)
  • 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
• [Presentation] Oct-3/4 induces CpG demethylation in the MGMT promoter to induce temozolomide resistance in glioblastoma cells (2013)
  • 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
• [Presentation] Oct-3/4 promotes migration and invasion of glioblastoma cells (2012)
  • 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
• [Presentation] Oct-3/4 promotes migration and invasion of glioblastoma cells (2012)
  • 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
• [Remarks]
  • URL: http://hgyano.jimdo.com/
• [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/
• [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
• [Remarks]
  • URL: http://www.proteo.ehime-u.ac.jp/section/06.html