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Analysis of the effects of hypoxia inducible factor for tumor metastasis

Research Project

Project/Area Number 24790308
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

YAMASHITA Toshiharu  筑波大学, 医学医療系, 助教 (50400677)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords分子腫瘍学 / 低酸素応答 / 血管内皮細胞 / がん微小環境 / がん転移
Research Abstract

Hypoxia inducible transcription factor (HIF) has various physiological functions. The results of the HIF functional analysis in vascular endothelial cells with tail vein injection metastasis model, we found that metastasis foci was reduced when transplanted into HIF-2alpah knockdown host mice. HIF-2alpa knockdown mice have low activities in HIF-2alpha in endothelial cells. Furthemore, HIF-3alpha acting on inhibitory to the hypoxic response is controlling to the inhibitory VE-cadherin expression in pulmonary vascular endothelial cells. We found the phenomenon that HIF-1apha is activated in compensatory when HIF-2alpha was reduced to a certain level below threshold.

Report

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

    (26 results)

All 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (18 results) Remarks (1 results)

  • [Journal Article] Dual Functions of Hypoxia - InducibleFactorlAlphaforthe Commitment of Mouse Embryonic Stem Cells Toward a Neural Lineage2014

    • Author(s)
      Zhao Y,Matsuo, Takasaki M,Tsuboi I,Kimura K,Salazar G.T.,Yamashita T,Ohneda O
    • Journal Title

      Stem Cells Dev

      Volume: 7 Issue: 3 Pages: 219-229

    • DOI

      10.1089/scd.2013.0328

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of NOX1/nicotinamide adenine dinucleotide phosphate, reduced form oxidase leads to pulmonary vascular remodeling.2014

    • Author(s)
      Iwata K, Ikami K, Matsuno K, Yamashita T, Shiba D, Ibi M, Matsumoto M, Katsuyama M, Cui W, Zhang J, Zhu K, Takei N, Kokai Y, Ohneda O, Yokoyama T, Yabe-Nishimura C.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 34(1) Issue: 1 Pages: 110-119

    • DOI

      10.1161/atvbaha.113.302107

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of CCL5 in the ability of adipose tissue-derived mesenchymal stem cells to support repair of ischemic regions.2014

    • Author(s)
      Kimura K, Nagano M, Salazar G, Yamashita T, Tsuboi I, Mishima H, Matsushita S, Sato F, Yamagata K, Ohneda O.
    • Journal Title

      Stem Cells Dev.

      Volume: 23(5) Issue: 5 Pages: 488-501

    • DOI

      10.1089/scd.2013.0307

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual Functions of Hypoxia-Inducible Factor 1 Alpha for the Commitment of Mouse Embryonic Stem Cells Toward a Neural Lineage2014

    • Author(s)
      Zhao Y, Matsuo-Takasaki M, Tsuboi I, Kimura K, Salazar GT, Yamashita T, Ohneda O.
    • Journal Title

      Stem Cells and Development

      Volume: 印刷中 Issue: 18 Pages: 2143-2155

    • DOI

      10.1089/scd.2013.0278

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional endothelial progenitor cells selectively recruit neurovascular protective monocyte-derived F4/80(+) /Ly6c(+) macrophages in a mouse model of retinal degeneration2013

    • Author(s)
      Fukuda S, Nagano M, Yamashita T, Kimura K, Tsuboi I, Salazar G, Ueno S, Kondo M, Kunath T, Oshika T, Ohneda O
    • Journal Title

      Stem Cells

      Volume: 31 Issue: 10 Pages: 2149-2161

    • DOI

      10.1002/stem.1469

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation2013

    • Author(s)
      Akimoto K, Kimura K, Nagano M, Takano S, To'a Salazar G, Yamashita T, Ohneda O.
    • Journal Title

      Stem Cells Dev

      Volume: 22 Issue: 9 Pages: 1370-1386

    • DOI

      10.1089/scd.2012.0486

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A subpopulation of endothelial progenitor cells with low aldehyde dehydrogenase activity attenuates acute ischemic brain injury in rats.2012

    • Author(s)
      Kazuhiro Nakamura, Hideo Tsurushima, Aiki Marushima, Masumi Nagano, Toshiharu Yamashita, Kensuke Suzuki, Osamu Ohneda, Akira Matsumura.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 418 Issue: 1 Pages: 87-92

    • DOI

      10.1016/j.bbrc.2011.12.139

    • NAID

      120007130720

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Deficient expression of HIF - 2a in spleen results in compensatory angiogenesis by up - regulated of HIF - la2013

    • Author(s)
      Ikki Tsuboi,Toshiharu Yamashita,Satomi Kobayashi,Osamu Ohneda
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト間葉系幹細胞のグリオブラストーマ増殖抑制に対する作用機構解明2013

    • Author(s)
      秋本恵子,木村健一,長野真澄,山下年晴,高野晋吾,大根田修
    • Organizer
      第l2回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 異なる歯組織形成段階における歯髄幹細胞の比較検討2013

    • Author(s)
      菊地豪,山系憲司,佐藤和聡,木村健一,山下年晴,大根田修
    • Organizer
      第l2回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] ステロイド薬投与による脂肪組織由来間葉系幹細胞への影響2013

    • Author(s)
      加藤俊貴,木村健一,長野真澄,山下年晴,秋本恵子,三島初,大根田修
    • Organizer
      第l2回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Deficient expression of HIF-2α in spleen results in compensatory angiogenesis by up-regulation of HIF-1 α2013

    • Author(s)
      Ikki Tsuboi, Toshiharu Yamashita, Satomi Kobayashi, Osamu Ohneda
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒト間葉系幹細胞のグリオブラストーマ増殖抑制に対する作用機構解明.2013

    • Author(s)
      秋本恵子,木村健一, 長野真澄, 山下年晴, 高野晋吾, 大根田修.
    • Organizer
      第12回 日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 異なる歯組織形成段階における歯髄幹細胞の比較解析2013

    • Author(s)
      菊地豪,山縣憲司,佐藤和聡,木村健一,山下年晴,大根田修.
    • Organizer
      第12回 日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] ステロイド薬投与による脂肪組織由来間葉系幹細胞への影響2013

    • Author(s)
      加藤俊貴,木村健一,長野真澄,山下年晴,秋本恵子,三島初,大根田修.
    • Organizer
      第12回 日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Hypoxia inducible factor - 3a regulates its target genes in association with HIF - la and HIF - 2a2012

    • Author(s)
      小林里美,山下年晴,長野真澄,木村健一,坪井一輝,大根田修
    • Organizer
      第l0回がんとハイポキシア研究会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Deficient expression of HIF - 2a in endothelial cell cause upregulation of HIF - la and compensatory angiogenesis2012

    • Author(s)
      坪井一輝,山下年晴,木村健一,小林里美,長野真澄,大根田修
    • Organizer
      第l0回がんとハイポキシア研究会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] HIF - la expression in ALDH - positive breast cancer is involved in cancer pogression2012

    • Author(s)
      白石章,木村健一,長野真澄,山下年晴,板東裕子,原尚人,大根田修
    • Organizer
      第l0回がんとハイポキシア研究会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 肺由来血管内皮細胞における低酸素応答転写因子HIF - 3aの機能解析2012

    • Author(s)
      小林里美,山下年晴,長野真澄,木村健一,大根田修
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] HIF - 2a kd/nullヘテロマウスを用いた造血機能解析2012

    • Author(s)
      坪井一輝,山下年晴,木村健一,大根田修
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Hypoxia inducible factor-3a regulates its target genes in association with HIF-1a and HIF-2a.2012

    • Author(s)
      小林里美,山下年晴,長野真澄,木村健一,坪井一輝,大根田修.
    • Organizer
      第10回 がんとハイポキシア研究会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] HIF-1a expression in ALDH-positive breast cancer is involved in cancer progression.2012

    • Author(s)
      白石章,木村健一,長野真澄,山下年晴,坂東裕子,原尚人,大根田修.
    • Organizer
      第10回 がんとハイポキシア研究会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Deficient expression of HIF-2a in endothelial cell cause upregulation of HIF-1a and compensatory angiogenesis.2012

    • Author(s)
      坪井一輝,山下年晴,木村健一,小林里美,長野真澄,大根田修.
    • Organizer
      第10回 がんとハイポキシア研究会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 肺由来血管内皮細胞における低酸素応答転写因子HIF-3aの機能解析2012

    • Author(s)
      小林里美,山下年晴,長野真澄,木村健一,大根田修.
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] HIF-2akd/nullヘテロマウスを用いた造血機能解析2012

    • Author(s)
      坪井一輝,山下年晴,木村健一,大根田修.
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Remarks] 所属研究室ホームページ

    • URL

      http://www.md.tsukuba.ac.jp/basic-med/remed/stemcell/index.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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