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造血幹細胞ニッチを介した癌の骨転移成立機構の解明

Research Project

Project/Area Number 20659295
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionMatsumoto Dental University

Principal Investigator

平賀 徹  Matsumoto Dental University, 歯学部, 准教授 (70322170)

Co-Investigator(Kenkyū-buntansha) 細矢 明宏  松本歯科大学, 歯学部, 講師 (70350824)
二宮 禎  松本歯科大学, 総合歯科医学研究所, 講師 (00360222)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2009: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2008: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords癌 / 骨転移 / 造血幹細胞ニッチ / N-カドヘリン
Research Abstract

骨への臓器特異的転移、および骨転移の成立・進展のメカニズム解明のために、本研究では骨転移における骨髄癌細胞ニッチの役割を明らかにすることを目的とし、「細胞接着分子を介した骨芽細胞と癌細胞の接着がニッチの形成に重要な役割を果たしている」との作業仮説を立てた。そのなかで、骨髄中の造血幹細胞ニッチの形成において、N-カドヘリンを介した骨芽細胞と造血幹細胞の接着が重要な役割を果たしていること、癌細胞のN-カドヘリンの発現が癌の悪性度と関連し、患者の予後と負の相関関係を示すことなどの報告から、特に細胞接着分子N-カドヘリンに注目し、研究を行った。昨年は、N-カドヘリンを過剰発現する癌細胞株、およびshRNAを用いたN-カドヘリンのノックダウン癌細胞株の樹立を行い、本年度は、これらの細胞を用い、in vivoの解析を行った。
1.N-カドヘリン過剰発現株およびノックダウン株のin vivoでの増殖能
N-カドヘリン過剰発現株およびノックダウン株の増殖能について、ヌードマウスへの移植により検討した結果、両者とも親株と比較して腫瘍増殖には差は認められなかった。
2.N-カドヘリン過剰発現株およびノックダウン株の骨転移能の比較
N-カドヘリン過剰発現株およびノックダウン株の骨転移能について、ヌードマウス左心室内移植モデルを用い検討した結果、こちらも両者とも親株と比較して腫瘍増殖には差は認められなかった。
今回のin vivoの実験結果からはいずれも癌細胞におけるN-カドヘリン発現の差異の影響を認めることは出来なかった。しかし、発現の増強および減弱の程度が十分であったかなどについては検討の余地があり、今後、継続して検討を進めていく予定である。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (54 results)

All 2010 2009 2008

All Journal Article (28 results) (of which Peer Reviewed: 23 results) Presentation (26 results)

  • [Journal Article] Zoledronic acid delays wound healing of the tooth extraction socket in mice : Insights into the pathogenesis of bisphosphonate-related osteonecrosis of the jaw.2010

    • Author(s)
      Kobayashi Y, et al.
    • Journal Title

      J Bone Miner Metab (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localization of Thy-1-positive cells in the perichondrium during endochondral ossification.2010

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Histochem Cytochem (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of bone-like mineralized matrix by periodontal ligament cells in vivo : a morphological study in rats.2009

    • Author(s)
      Hiraga T, et al.
    • Journal Title

      J Bone Miner Metab 27

      Pages: 149-157

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imatinib mesylate suppresses bone metastases of breast cancer by inhibiting osteoclasts through the blockade of c-Fms signals.2009

    • Author(s)
      Hiraga T, et al.
    • Journal Title

      Int J Cancer 124

      Pages: 215-222

    • Related Report
      2009 Annual Research Report 2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo.2009

    • Author(s)
      Mizoguchi T, et al.
    • Journal Title

      J Cell Biol 184

      Pages: 541-554

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diphenylhydantoin inhibits osteoclast differentiation and function through suppression of NFATc1 signaling.2009

    • Author(s)
      Koide M, et al.
    • Journal Title

      J Bone Miner Res 24

      Pages: 1469-1480

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The light and dark side of bisphosphonates.2009

    • Author(s)
      Jimi E, et al.
    • Journal Title

      J Oral Biosci 51

      Pages: 177-187

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of p63 during early craniofacial development of the mouse embryo.2009

    • Author(s)
      Hosoya A, et al.
    • Journal Title

      Dev Reprod 13

      Pages: 89-95

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chick tooth induction revisited.2009

    • Author(s)
      Cai J, et al.
    • Journal Title

      J Exp Zoolog B Mol Dev Evol 312

      Pages: 465-472

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ERK activation is involved in tooth development via FGF10 signaling.2009

    • Author(s)
      Cho KW, et al.
    • Journal Title

      J Exp Zoolog B Mol Dev Evol 312

      Pages: 901-911

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intermittent parathyroid hormone administration stimulates preosteoblastic proliferation without leading to enhanced bone formation in osteoclast-less c-fos(-/-)mice.2009

    • Author(s)
      de Freitas PH, et al.
    • Journal Title

      J Bone Miner Res 24

      Pages: 1586-1597

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A local bone anabolic effect of rhFGF2-impregnated gelatin hydrogel by promoting cell proliferation and coordinating osteoblastic differentiation.2009

    • Author(s)
      Kodama N, et al.
    • Journal Title

      Bone 44

      Pages: 699-707

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of pharmaceuticals with a novel fifty-hour animal model of bone loss.2009

    • Author(s)
      Yoshiya T, et al.
    • Journal Title

      J Bone Miner Res 24

      Pages: 1194-1205

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An in vivo 3D micro-CT evaluation of tooth movement after the application of different force magnitudes in rat molar.2009

    • Author(s)
      Gonzales C, et al.
    • Journal Title

      Angle Orthodontist 79

      Pages: 703-714

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 歯の形態形成を制御する分子に関する最近の知見2009

    • Author(s)
      平賀徹
    • Journal Title

      歯界展望 114

      Pages: 610-611

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 歯根膜幹細胞を用いた歯周組織再生2009

    • Author(s)
      細矢明宏
    • Journal Title

      THE BONE 23

      Pages: 108-109

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 歯髄を用いた再生療法の試み2009

    • Author(s)
      細矢明宏
    • Journal Title

      歯界展望 113

      Pages: 1174-1175

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Formation of bone-like mineralized matrix by periodontal ligament cells in vivo : a morphological study in rats.2009

    • Author(s)
      Hiraga T, et al.
    • Journal Title

      J Bone Miner Metab (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chick tooth induction revisited.2009

    • Author(s)
      Cai J, et al.
    • Journal Title

      Int J Dev Biol (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 3D micro-CT evaluation of tooth movement after the application of different force magnitudes in rat molar in vivo.2009

    • Author(s)
      Gonzales C, et al.
    • Journal Title

      Angle Orthodontist (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of cell-cell and cell-matrix interactions in bone destruction induced by the metastatic MDA-MB-231 human breast cancer cells in nude mice.2008

    • Author(s)
      Nakamura H, et al.
    • Journal Title

      J Bone Miner Metab 26

      Pages: 642-647

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cadherin-1 1-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast ancer cells in bone.2008

    • Author(s)
      Tamura D, et al.
    • Journal Title

      Int J Oncol 33

      Pages: 17-24

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alveolar bone regeneration of subcutaneously transplanted ratmolar.2008

    • Author(s)
      Hosoya A, et al.
    • Journal Title

      Bone 42

      Pages: 350-357

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BMP4 signaling regulates formation of Hertwig's epithelial rootsheath during tooth root development.2008

    • Author(s)
      Hosoya A, et al.
    • Journal Title

      Cell Tissue Res 333

      Pages: 503-509

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological evidence of basal keratinocyte migration during the re-epithelialization process.2008

    • Author(s)
      Hosoya A, et al.
    • Journal Title

      Histochem Cell Biol 130

      Pages: 1165-1175

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of BMP4 in HERS during tooth root development.2008

    • Author(s)
      Jung HS, et al.
    • Journal Title

      J Oral Biosci 50

      Pages: 160-166

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 歯根膜組織の歯槽骨再生能2008

    • Author(s)
      細矢明宏ら
    • Journal Title

      THE BONE 22

      Pages: 3-7

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 骨転移による骨破壊現象における細胞間,細胞基質問作用の重要性2008

    • Author(s)
      中村浩彰ら
    • Journal Title

      THE BONE 22

      Pages: 575-579

    • Related Report
      2008 Annual Research Report
  • [Presentation] 卵巣摘出マウスの骨密度低下に対するホノキオールの抑制効果2010

    • Author(s)
      浅井みどり, ら
    • Organizer
      日本農芸化学会 2010年度大会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 卵巣摘出マウスの骨密度低下に対するエピガロカテキンガレートの抑制効果2010

    • Author(s)
      李順燕, ら
    • Organizer
      日本農芸化学会 2010年度大会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] OPG遺伝子欠損マウスの歯槽骨吸収に対する骨吸収抑制剤の効果2009

    • Author(s)
      小出雅則, ら
    • Organizer
      第69回 松本歯科大学学会
    • Place of Presentation
      長野
    • Year and Date
      2009-11-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] in-vivo Micro CTの骨研究における有用性2009

    • Author(s)
      二宮禎
    • Organizer
      第9回 日本外傷歯学会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Rapid evaluation of a denosumab-like anti-human RANKL neutralizing monoclonal antibody with sRANKL treated bone loss model.2009

    • Author(s)
      Yasuda H, et al.
    • Organizer
      31st Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Colorado, USA
    • Year and Date
      2009-09-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] Treatment with bisphosphonate during tooth development inhibits tooth formation and eruption, and induces odontomas2009

    • Author(s)
      Hiraga T, et al.
    • Organizer
      31st Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Colorado, USA
    • Year and Date
      2009-09-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] 歯根膜組織の歯槽骨再生能2009

    • Author(s)
      細矢明宏
    • Organizer
      第51回 歯科基礎医学会学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 骨芽細胞分化におけるSUMO化修飾因子UBC9の役割2009

    • Author(s)
      雪田聡, ら
    • Organizer
      第51回 歯科基礎医学会学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト歯髄組織におけるFibrillin-1の分解が細胞分化および石灰化に及ぼす影響2009

    • Author(s)
      吉羽永子, ら
    • Organizer
      第51回 歯科基礎医学会学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] OPG遺伝子欠損マウスにおいては著しい歯槽骨吸収を呈する2009

    • Author(s)
      小出雅則, ら
    • Organizer
      第51回 歯科基礎医学会学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] in-vivo Micro CTの骨研究における有用性2009

    • Author(s)
      二宮禎
    • Organizer
      第1回 In-vivo micro CT forum
    • Place of Presentation
      長野
    • Year and Date
      2009-08-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] 骨膜のThy-1(CD90)陽性細胞の骨原性細胞としての役割2009

    • Author(s)
      中村浩彰, ら
    • Organizer
      第27回 日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] RANKL投与骨量減少症モデルマウスによるdenosumab様抗ヒトRANKL中和抗体の迅速評価2009

    • Author(s)
      富盛賀也, ら
    • Organizer
      第27回 日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 歯胚形成期のビスフォスフォネート投与は歯の形成・萌出を生害し,歯牙腫様病変を誘発する2009

    • Author(s)
      平賀徹, ら
    • Organizer
      第27回 日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 骨吸収関連遺伝子改変マウスにおける歯槽骨吸収及びビスフォスフォネートの効果2009

    • Author(s)
      小出雅則, ら
    • Organizer
      第27回 日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト歯髄組織におけるFibrillin-1の局在に関する免疫組織化学的研究-石灰化および細胞分化との関連性について-2009

    • Author(s)
      吉羽永子, ら
    • Organizer
      第130回 日本歯科保存学会・春季学会
    • Place of Presentation
      北海道
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] In vivoマイクロCTを用いた骨形態解析2009

    • Author(s)
      二宮禎
    • Organizer
      第29回 日本骨形態計測学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Minocyclineが樹状細胞と破骨細胞分化に及ぼす影響2008

    • Author(s)
      衣川 さやら
    • Organizer
      第26回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2008-10-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 歯根膜細胞による歯周組織形成能2008

    • Author(s)
      平賀 徹ら
    • Organizer
      第26回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2008-10-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 歯根膜Side Population細胞を用いた歯槽骨再生の試み2008

    • Author(s)
      二宮 禎ら
    • Organizer
      第26回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2008-10-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 低分子量GタンパクRaplはMEK-ERK経路の活性化を介して骨芽細胞分化を促進する2008

    • Author(s)
      上田 晃己ら
    • Organizer
      第26回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] 歯根膜細胞のin vivoにおける骨形成能2008

    • Author(s)
      平賀 徹ら
    • Organizer
      第50回歯科基礎医学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] 歯根膜sp細胞を用いた歯槽骨再生の試み2008

    • Author(s)
      二宮 禎ら
    • Organizer
      第50回歯科基礎医学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] ビスフォスフォネートの抗腫瘍作用とそのメカニズム2008

    • Author(s)
      平賀 徹ら
    • Organizer
      第50回歯科基礎医学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] The small G-protein Rapl promotes osteoblast differentiation.2008

    • Author(s)
      Ueda A, et al.
    • Organizer
      30^<th> Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2008-09-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] Osteogenic potential of periodontal ligament cells in vivo.2008

    • Author(s)
      Hiraga T., et al.
    • Organizer
      30^<th> Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2008-09-14
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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