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前哨リンパ節への癌転移因子解明のリンパ生理学的研究

Research Project

Project/Area Number 15659310
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionShinshu University

Principal Investigator

大橋 俊夫  国立大学法人信州大学, 医学部, 教授 (80020832)

Co-Investigator(Kenkyū-buntansha) 伊古美 文隆  国立大学法人信州大学, 医学部, 助教授 (50262704)
水野 理介  国立大学法人信州大学, 医学部, 講師 (30273080)
河合 佳子  国立大学法人信州大学, 医学部, 助手 (10362112)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordslymphatic endothelial cells / culture / adhesion molecules / lymph angiogenesis / lymphatic metastasis / sentinel lymph node / intalvital microscope / hypoxia / tumor microcirculation / PO_2 in the lymph / pH in the lymph / limph angiogenesis / limphatic metastasis / lymph node
Research Abstract

リンパ管内皮細胞に発現する細胞接着因子の解明と腫瘍細胞との相互作用を解析した。
1.ラット、マウス胸管ならびに末梢の集合リンパ管におけるリンパ管内皮細胞の培養システムを確立した。
2.培養リンパ管内皮細胞に発現する接着因子をcadherin、selectin、immunoglobulin、superfamily等ごとに分子生物学ならびに免疫組織化学的手法を用いて体系的に解析し、生理的状態でリンパ管内皮細胞にE-selectinが特異的に発現していることを見い出した。さらに炎症性サイトカインTWFαやIL-1β刺激でその接着因子の発現は特異的に増強することを発見した。
3.腫瘍細胞、活性化マクロファー一ジ、Tリンパ球ならびにNK細胞と上記2で解析した細胞接着因子との相互作用とリンパ動態に及ぼす影響を摘出リンパ節標本の生体顕微鏡システムを用いて解析した。その結果、生体内でリンパ管内皮細胞と自家リンパ球の接着に流れ因子の影響がきわめて強いことを見い出した。
4.以上の結果を基に、現在ヒト胃癌細胞の悪性株とリンパ管内皮細胞の間に特異的に発現している接着因子を探査し、その接着因子のクローニングを開始し、予備実験レベルで新規接着因子の関与を示唆する知見を得ている。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (10 results)

All 2005 2004 Other

All Journal Article (5 results) Publications (5 results)

  • [Journal Article] Current topics in physiology and pharmacology of lymph vessels.2005

    • Author(s)
      Ohhashi, T., Mizuno, R., Ikomi, F., Kawai, Y.
    • Journal Title

      Pharmacology and Therapeutics 105

      Pages: 165-188

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of NO and EDHF on flow-induced vasodilation in isolated hamster cremasteric arterioles.2005

    • Author(s)
      Watanabe, S., Yashiro, Y., Mizuno, R., Ohhashi, T.
    • Journal Title

      Journal of Vascular Research 42

      Pages: 137-147

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Lymphodynamic properties governing sentinel lymph node.2004

    • Author(s)
      Ohhashi, T.
    • Journal Title

      Annul Surgical Oncology 11

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ATP inhibits pump activity of lymph vessels via adenosine A1 receptors-mediated involvement of nitric oxide and ATP-sensitive K+ channels.2004

    • Author(s)
      Kousai, A., Mizuno, R., Ikomi, F., Ohhashi T.
    • Journal Title

      American Journal of Physiology 287

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.2004

    • Author(s)
      Cao, R.H., Bjorndahl, M.A., Relgar, P., et al.
    • Journal Title

      Cancer Cell 6

      Pages: 333-345

    • Related Report
      2004 Annual Research Report
  • [Publications] Mizuno, R.: "Establishment of rat lymphatic endothelial cell line."Microcirculation. 10. 127-131 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hosaka, K.: "Rho-Rho kinase pathway is involved in the regulation of myogenic tone and pump activity in isolated lymph vessels."American Journal of Physiology. 284. H2015-H2025 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsunemoto, H.: "Flow-mediated release of nitric oxide from lymphatic endothelial cells of pressurized canine thoracic duct."Japanese Journal of Physiology. 53. 157-163 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Momoi, H.: "Estrogen-induced augmentation of endothelium-dependent nitric oxide-mediated vasodilation in isolated rat cerebral small arteries."Japanese Journal of Physiology. 53. 193-203 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yashiro, Y.: "Age-dependent changes in regulatory roles of nitric oxide and prostanoids on mechanical activities of rabbit spinal arterioles."Japanese Journal of Physiology. 53. 335-342 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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