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Regulatory mechanism of membrane coreceptors in the proliferation of human myeloma cells

Research Project

Project/Area Number 14370305
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionYamaguchi University

Principal Investigator

KAWANO Michio  Yamaguchi University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40161343)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Hideaki  Yamaguchi University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (40294623)
OBATA Masanori  Yamaguchi University, School of Medicine, Assistant Profssor, 医学部, 講師 (80158831)
TSUYAMA Naohiro  Yamaguchi University, Graduate School of Medicine, Research Associate, 大学院・医学研究科, 助手 (10335747)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsmyeloma / IL-6 / CD45 / lipid rafts / immature myeloma cells / CD45 isoform / フォスファターゼ / 骨髄腫細胞 / CD19 / ラフト / 細胞膜分子動態
Research Abstract

In multiple myeloma, there are quite diffrences in the surface expression of membrane proteins compared with those of normal plasma cells. Especially, a restricted number of myeloma cells express CD45 molecules and CD45RO, while normal plasma cells express CD45 and CD45RA. In addition, myeloma cells that can respond to IL-6 to proliferate are CD45-positive (CD45+) immature Myeloma cells, while CD45-negative(CD45-) Myeloma cells cannot respond to IL-6 to proliferate.
In this study, we tried to clarify the role of CD45 molecules on IL-6-induced proliferation in human Myeloma cells, especially to examine the differences in their movement of CD45 isoforms after IL-6 stimulation.
From this study, we found that CD45 molecules located outside lipid rafts without IL-6 stimulation, but after IL-6 stimulation CD45RO but not CD45RA moved to lipid rafts rapidly. Furthermore, we confirmed that CD45RO molecule moving to lipid rafts functioned as activator of Lyn by dephosphorylation of Tyr507 of Lyn. These results could explain why CD45+ myeloma cells(CD45RO+) but not normal plasma cells(CD45RA+) can respond to IL-6 to proliferate. In future, these results also contribute to the progress in the molecular target therapy in human myeloma.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (35 results)

All 2005 2004 2003 2002 Other

All Journal Article (18 results) Book (2 results) Publications (15 results)

  • [Journal Article] A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma2005

    • Author(s)
      Li F
    • Journal Title

      BLOOD 105

      Pages: 3295-3302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A rapid translocation of CD45RO but not CD45RA to lipid rafts in IL-6-induced proliferation in myeloma.2005

    • Author(s)
      Li F, et al.
    • Journal Title

      Blood 105

      Pages: 3295-3302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A rapid translocation of CD45RO but not CD45RA to lipid rafys in IL-6-induced proliferation in myeloma2005

    • Author(s)
      Li F
    • Journal Title

      BLOOD 105・8

      Pages: 3295-3302

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 骨髄腫:病態の理解と新しい治療法 骨髄腫細胞は形質細胞とどこが違うのか?2005

    • Author(s)
      大津山賢一郎
    • Journal Title

      分子細胞治療 4・1

      Pages: 3-10

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Receptor synergy of interleukin-6 (IL-6) and insulin-like growth factor-I in Myeloma cells that highly express IL-6 receptor alpha2004

    • Author(s)
      Abroun S
    • Journal Title

      BLOOD 103

      Pages: 2291-2298

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 多発性骨髄腫と類縁疾患 1.骨髄腫細胞の増殖機構2004

    • Author(s)
      河野道生
    • Journal Title

      血液フロンテイア 14

      Pages: 1499-1504

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Receptor synergy of interleukin-6(IL-6) and insulin-like growth factor-I in Myeloma cells that highly express IL-6 receptor alpha.2004

    • Author(s)
      Abroun S, et al.
    • Journal Title

      Blood 103

      Pages: 2291-2298

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Growth mechanism of myeloma cells2004

    • Author(s)
      Kawano MM.
    • Journal Title

      Hematology Frontier 14

      Pages: 1499-1504

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Receptor synergy of interleukin-6(IL-6) and insulin-like growth factor-I in Myeloma cells that highly express IL-6 receptor alpha.2004

    • Author(s)
      Abroun S
    • Journal Title

      BLOOD 103・6

      Pages: 2291-2298

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 多発性骨髄腫の病態と分子標的療法 増殖機序2004

    • Author(s)
      河野道生
    • Journal Title

      血液・腫瘍科 48・3

      Pages: 243-249

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 多発性骨髄腫と類縁疾患 1.骨髄腫細胞の増殖機構2004

    • Author(s)
      河野道生
    • Journal Title

      血液フロンティア 14・10

      Pages: 1499-1504

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Multiple myeloma and related diseases2003

    • Author(s)
      Kawano MM.
    • Journal Title

      Internal Medicne (Bunkoudou, Tokyo)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Requirement of src family kinase activity associated with CD45 for Myeloma cell proliferation by interleukin-62002

    • Author(s)
      Ishikawa H
    • Journal Title

      BLOOD 90

      Pages: 2172-2178

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 多発性骨髄腫-最近の進歩2002

    • Author(s)
      河野道生
    • Journal Title

      Excerpta Medica 18

      Pages: 4-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 内科-100年のあゆみ(血液)III.主要疾患の歴史 8.多発性骨髄腫2002

    • Author(s)
      河野道生
    • Journal Title

      日本内科学会雑誌 91

      Pages: 2106-2113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Requirement of src family kinase activity associated with CD45 for Myeloma cell proliferation by interleukin-62002

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

      Blood 99

      Pages: 2172-2178

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recent Progress in Multiple Myeloma2002

    • Author(s)
      Kawano MM.
    • Journal Title

      Excerpta Medica 18

      Pages: 4-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multiple Myeloma in 100^<th> anniversary2002

    • Author(s)
      Kawano MM.
    • Journal Title

      The Journal of the Japanese Society of Internal Medicine 91

      Pages: 2106-2113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Annual Review 2004 血液2004

    • Author(s)
      石川 秀明
    • Total Pages
      8
    • Publisher
      中外医学社
    • Related Report
      2004 Annual Research Report
  • [Book] 内科学(多発性骨髄腫とその類縁疾患)2003

    • Author(s)
      河野道生
    • Total Pages
      6
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Saeid Abroun: "Receptor synergy of interleukin-6(IL-6) and insulin-like growth factor-I in the IL-6 receptor α highly expressing myeloma cells"Blood. 103・6. 2291-2298 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naohiro Tsuyama: "The regulatory mechanism of IL-6-dependent proliferation of human myeloma cells"Hematology. 8・6. 409-411 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideaki Ishikawa: "Interleukin-6, CD45, and the src-kinases in myeloma cell proliferation"Leukemia and Lymphoma. 44・9. 1477-1481 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideaki Ishikawa: "Interleukin-6-induced proliferation of human myeloma cells associated with CD45 molecules"International Journal of Hematology. 78・2. 95-105 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 河野道生: "II(第内科学2版)第8章 血液・造血器疾患"文光堂. 6 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 石川秀明: "Annual Review 血液 2004"中外医学社. 9 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 河野道生: "造血器悪性腫瘍治療へのアプローチ"医薬ジャーナル社. 15 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikawa H: "Requirement of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6"Blood. 99. 2172-2178 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishikawa H: "CD19 expression and growth inhibition of tumours in human multiple myeloma"Leuk Lymphom. 43. 613-616 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河野 道生: "多発性骨髄腫-最近の進歩"Currents in Hematoimmunology. 18. 4-9 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河野 道生: "Mタンパク血症の概念-骨髄腫とMGUS(良性Mタンパク血症)-"血液フロンティア. 12. 577-581 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河野 道生: "検査計画法 血液疾患編 9. 血漿蛋白異常症"綜合臨床. 51. 1719-1723 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河野 道生: "特集 内科100年のあゆみ(血液) III.主要疾患の歴史 8.多発性骨髄腫"日本内科学会雑誌. 91. 152-159 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河野 道生: "エッセンシャル血液病学"柴田 昭, 池田康夫, 朝長万左男, 堀田知光. 277 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 河野 道生: "シュミレーション内科 血液疾患を探る"別所正美, 金倉 譲. 230 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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