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がん幹細胞の自己複製を抑制する分子標的の解明

Research Project

Project/Area Number 19659078
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionOsaka University

Principal Investigator

高倉 伸幸  Osaka University, 微生物病研究所, 教授 (80291954)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords癌 / 発生分化 / 自己複製 / ニッチ / 幹細胞 / がん幹細胞
Research Abstract

現在癌治療の標的とされる細胞は、癌細胞を産生する癌幹細胞とその生存増殖を支持するストロマ細胞である。そこで癌幹細胞の腫瘍組織内における局在を明らかにすることが、この両者の細胞間相互作用を営む分子標的の探索にとっては重要である。従来の癌幹細胞の同定手段としては、蛍光標識したlipophilic dyeを効率良く排出する機能を利用してフローサイトメトリー法で、蛍光色素に染色されない細胞集団(side population;SP細胞)として分画する方法が応用されてきているが、この方法では腫瘍組織の癌幹細胞の局在を解析することは困難である。本研究では癌幹細胞に発現する可能性が高いDNA複製因子であるPSF1遺伝子やSLD5遺伝子の発現を腫瘍組織内でライブイメージを観察し、癌幹細胞の局在を明らかにすることを目的に研究を遂行した。腫瘍細胞中のPSF1遺伝子プロモーター制御下にEGFPを発現する癌細胞を用いて解析したところ、EGFP発現強度の高い癌細胞は、細胞増殖および転移能ともにEGFP弱陽性細胞に比べ活性が高く、このようなEGFP強陽性細胞は腫瘍周囲の血管領域に多く観察された。またSLD5遺伝子座にLacZをノックインしたES細胞を用いて行った奇形腫モデルでも、PSF1の結果と同様、SLD5の転写活性の高いLacZ強陽性細胞は再移植可能な奇形腫癌幹細胞であり、これらも血管領域に高頻度に観察された。以上から、癌幹細胞はニッチとして血管領域を利用していることが示唆された。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (36 results)

All 2009 2008 2007 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (16 results) Remarks (1 results)

  • [Journal Article] Both alleles of PSF1 are required for maintenance of pool sizeof immature hematopoietic cells and acute bone marrowregeneration.2009

    • Author(s)
      Ueno M
    • Journal Title

      Blood 113

      Pages: 555-562

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] spatial and temporal role of the apelin/APJ system inthe calibersize regulation of blood vessels during angiogenesis.2008

    • Author(s)
      Kidoya H
    • Journal Title

      EMBO J. 27

      Pages: 522-534

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of MDR1 Function In Proliferation of Tumor Cells.2008

    • Author(s)
      Katoh SY
    • Journal Title

      J Biochem. 143

      Pages: 517-524

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1.2008

    • Author(s)
      Fukuhara S
    • Journal Title

      Nat Cell Biol. 10

      Pages: 513-526

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of platelet-derived growth factor receptor-beta inmaintenance of mesenchyme and sensory epithelium of theneonatal mouse inner ear.2008

    • Author(s)
      Hayashi H
    • Journal Title

      Hear Res. 245

      Pages: 73-81

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiopoietin-1 alters tumor growth by stabilizing blood vesselsor by promoting angiogenesis.2008

    • Author(s)
      Satoh N
    • Journal Title

      Cancer Sci. 99

      Pages: 2373-2379

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis2008

    • Author(s)
      Kidoya H
    • Journal Title

      EMBO J. 27

      Pages: 522-534

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EphB4 overexpression on B16 melanoma cells affects arterial-venous patterning in tumor angiogenesis.2007

    • Author(s)
      Huang X
    • Journal Title

      Cancer Res. 67

      Pages: 9800-9808

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death.2007

    • Author(s)
      Iwanaga A
    • Journal Title

      Neurosci Lett. 429

      Pages: 43-48

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow non-hematopoietic cells to differentiate into cardiomyocytes.2007

    • Author(s)
      Yamada Y
    • Journal Title

      Stem cells 25

      Pages: 1326-1333

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue.2007

    • Author(s)
      Yamada Y
    • Journal Title

      Biochem Biophys Res Commun. 353

      Pages: 182-188

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of angiogenic and neurotrophic factors in the progenitor cell niche of adult monkey subventricular zone.2007

    • Author(s)
      Tonchev AB
    • Journal Title

      Neuroscience 144

      Pages: 1425-1435

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential Roles of the CC Chemokine Ligand 3-CC Chemokine Receptor 5 Axis in Bleomycin-Induced Pulmonary Fibrosis through Regulation of Macrophage and Fibrocyte Infiltration.2007

    • Author(s)
      Ishida Y
    • Journal Title

      Am J Pathol. 170

      Pages: 843-854

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Axonal Outgrowth in the Tumor Environment:Involvement of Class 3 Semaphorins.2007

    • Author(s)
      Vachkov IH
    • Journal Title

      Cancer Sci. 98

      Pages: 1192-1197

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse:involvement of tenascin-C induced by aldosterone-mediated inflammation.2007

    • Author(s)
      Nishioka T
    • Journal Title

      J Cardiovasc Pharmacol 49

      Pages: 261-268

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maturation of blood vessels by haematopoietic stem cells andprogenitor cells : involvement of apelin/APJ and Angiopoietin/Tie2 interactions in vessel caliber size regulation.

    • Author(s)
      Takakura N
    • Journal Title

      Thrombosis and Haemostasis (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction and expression of anti-angiogenic vasohibins in thehematopoietic stem/progenitor cell population.

    • Author(s)
      Naito H
    • Journal Title

      J Biochem. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of stem cell-specifictranscription of PSFl in spermatogenesis.

    • Author(s)
      Han Y
    • Journal Title

      Biochem Biophys Res Commun. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of MDR1 Function In Proliferation of Tumor Cells.

    • Author(s)
      Katoh SY
    • Journal Title

      J Biochem. inpress

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Visualization of Cancer Stem Cell and Their Niche.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      Conference on Protein Modification and Disease.
    • Place of Presentation
      Seoul, Republic of Korea
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] Analysis of Blood Vessel Maturation : Involvement of Apelin/APJ and Angiopoietin/Tie2 Interactions and EndothelialStem Cell System.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      第24回熊本医学・生物科学シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2008-11-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] 血管新生の基礎と臨床的進歩2008

    • Author(s)
      高倉伸幸
    • Organizer
      日本血液学会総会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] Tie2 alters tumor growth by stabilizing blood Vessels orpromoting angiogenesis.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      第67回日本癌学会学術総会(International Session)
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Visualization of cancer stem cells and vascular niche formation.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      第67回日本癌学会学術総会(Symposium)
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular analysis of Tie2 receptor in angiogenesis.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      第16回日本血管生物医学会学術集会・The 6^(th) Korea-Japan Joint Symposium on Vascular Biology合同学術集会
    • Place of Presentation
      金沢
    • Related Report
      2008 Annual Research Report
  • [Presentation] Maturation of Blood Vessels by Hematopoietic Stem Cells.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      The 15^(th) International Vascular Biology Meeting
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2008 Annual Research Report
  • [Presentation] Maturation of Blood Vessels by Hematopoietic Stem Cells.2008

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      The 9^(th) International Conference on Angiogenesis : Basic Science and ClinicalApplications
    • Place of Presentation
      Patras, Greece
    • Related Report
      2008 Annual Research Report
  • [Presentation] Galectin-3 induces quiescence of hematopoietic stem cells in the bone marrow niche.2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      1stInternational Cell Therapy Symposium in Korea
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2007-11-16
    • Related Report
      2007 Annual Research Report
  • [Presentation] Involvement of hematopoietic stem cell population in angiogenesis.2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      7th ESH Euroconference on Angiogenesis.
    • Place of Presentation
      Albufeira, Portugal
    • Related Report
      2007 Annual Research Report
  • [Presentation] Process of blood vessel maturation in physiological and pathological condition.2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      19th FAOBMB Seoul Conference.
    • Place of Presentation
      Seoul, Republic of Korea
    • Related Report
      2007 Annual Research Report
  • [Presentation] Arterial and venous specification in pathological and physiological angiogenesis.2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      Japan-Korea Joint Symposium on Vascular Biology
    • Place of Presentation
      Chuncheon, Korea
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular analysis of stemness and blood vessel formation regulated by Tie2.2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      The First Pacific Symposium on Angiogenesis and Lymphangiogenesis.
    • Place of Presentation
      Jeju Island Convention Center, Korea
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular analysis of blood vessel maturation2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      The Joint Meeting of Vascular Biology Organizations in Asia Pacific Region.
    • Place of Presentation
      Tainan, Taiwan
    • Related Report
      2007 Annual Research Report
  • [Presentation] レセプター型チロシンキナーゼTie2による血管新生の制御機構2007

    • Author(s)
      高倉伸幸
    • Organizer
      第30回 日本分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Maturation of blood vessels in the tumor.2007

    • Author(s)
      Nobuyuki Takakura
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.biken.osaka-u.ac.jp/act/act_takakura.php

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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