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癌随伴線維芽細胞を標的としたがん治療法の開発

Research Project

Project/Area Number 20015038
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionSapporo Medical University

Principal Investigator

瀧本 理修  Sapporo Medical University, 医学部, 講師 (10336399)

Co-Investigator(Kenkyū-buntansha) 佐藤 康史  札幌医科大学, 医学部, 講師 (80343383)
高田 弘一  札幌医科大学, 医学部, 助教 (90398321)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2009: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2008: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsCAF / DDS / targeting / 細胞標的治療 / がん随伴線維芽細胞
Research Abstract

【目的】癌の治療戦略として注目されているがん間質に対する治療法を開発する目的で本研究を行った。【背景】がん随伴細胞(CAF)が癌細胞より分泌された種々の増殖因子により線維芽細胞より変態した筋線維芽細胞に類似したものであることから、肝星細胞と同様にVitamin Aを取り込む性質を持つことに着目した。
【方法および結果】平成20年度はVA-liposomeを作製し(Sato Y, Takimoto R, Nat Biotech 2008)、in vitroでのCAFへの導入効率を検討し、VAとリポゾームのratioなど効率的な送達を目指した。また、乳癌細胞、大腸癌細胞など各種癌細胞株とCAFの共培養系を確立し、抗がん剤を搭載したVA-リポゾームによる細胞障害性を検討した。これらのin vitroの結果では、VA-リポゾームはCAF特異的に抗がん剤を送達し、CAFの障害により間接的にがん細胞の増殖も抑制しうること示した。そのうえで、平成21年度はプロトタイプのVA-リポゾームを作製し、これに標識化合物(siRNA, plasmid DNAなど)を封入しin vivoで担癌マウスに尾静脈から投与し、in vivo image analyzerで解析した。その結果、CAFのみならずCAFを通じて癌細胞へも特異的に標識化合物を送達しうることを確認した。現在、これらの結果を踏まえて、抗がん剤を搭載したVA-リポゾームを開発し、抗腫瘍効果の増強による新しい細胞治療を目論んで準備を進めている。

Report

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

    (11 results)

All 2009 2008

All Journal Article (11 results) (of which Peer Reviewed: 11 results)

  • [Journal Article] Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unressectable metastatic gastric cancer.2009

    • Author(s)
      Sato Y, Takimoto R, et al.
    • Journal Title

      Cancer Chemother Pharmacol.

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms.2009

    • Author(s)
      Hayashi T, Takimoto R, et al.
    • Journal Title

      J Gastroenterol. 44

      Pages: 964-975

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug resistance is dramatically restored by hedgehog inhibitors in CD3 4+ leukemic cells.2009

    • Author(s)
      Kobune M, Takimoto R
    • Journal Title

      Cancer Sci. 100(5)

      Pages: 948-955

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant crypt foci as precursors of the dysplasia-carcinoma sequence in patients with ulcerativecolitis2008

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

      Clin Cancer Res 14(1)

      Pages: 48-54

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination therapy of an anti-cancer drug with the FNIII14 pe ptide of fibronectin effectively overcomes cell adhesion mediated-drug resistance of acute myelogenous leukemia2008

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

      Leukemia 22(2)

      Pages: 353-360

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenoviral vector-mediated transfer of the Indian hedgehog gene modulates lymphomyelopoiesis in vivo2008

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

      Stem Cells 26(2)

      Pages: 534-542

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resolution of liver cirrhosis using vitamin A-coupled liposomes t o deliver siRNA against a collagen-specific chaperone2008

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

      Nat Biotechnol 26(4)

      Pages: 431-442

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jur kat cells by cleavage of receptor-interacting protein and inhibitio n of lysosomal cathepsin2008

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

      J Immunol 181(1)

      Pages: 197-207

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPe p/p53, and 5-fluorouracil in mice2008

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

      Hepatology 48(3)

      Pages: 828-840

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction with human stromal cells enhances CXCR4 expressio n and engraftment of cord blood Lin(-)CD34(-) cells2008

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

      Exp Hematol 36(9)

      Pages: 1121-1131

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo large-scale generation of human red blood cells from cor d blood CD34+ cells by co-culturing with macrophages2008

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

      Int J Hematol 87(4)

      Pages: 339-350

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed

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Published: 2008-04-01   Modified: 2018-03-28  

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