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Growth Regulation of Human Myeloma cells: Regulatory Mechanism in the bone marrow microenvironment.

Research Project

Project/Area Number 03454525
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

KAWANO Michio  Hiroshima University Hospital, Assistant Professor, 医学部・附属病院, 講師 (40161343)

Co-Investigator(Kenkyū-buntansha) KURAMOTO Atsushi  Research Institute for Nuclear Medicine and Biology, Hiroshima University, Profe, 原爆放射能医学研究所, 教授 (50034070)
TANABE Osamu  Hiroshima University School of Medicine, Research Associate, 医学部, 助手 (70221398)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsMyeloma / Myeloma cells / Adhesion molecules / Integrin / Stromal cells / Precursor cells / Monoclonal antibody / Cell sorter / 骨髄ストロ-マ細胞 / モノクロ-ナル抗体
Research Abstract

Since myeloma cells reside in the bone marrow, we investigated the role of microenvironment in the bone marrow on growth of myeloma cells. First, we examined the expression of adhesion molecules on myeloma cells by two-color analysis using anti-CD38 antibody. We found that all myeloma cells located at CD38-strong positive fraction and identified two subpopulations; VLA-5-MPC-1- myeloma cells and VLA-5+MPC-1+ myeloma cells. By a cell sorter,each fraction was isolated and followed by examining the morphology, in vitro proliferative activity and M-protein secretion. These revealed that VLA-5- immature myeloma cells proliferated markedly and responded to interleukin 6(IL-6), while VLA-5+ mature myeloma cells showed low proliferative activities but secreted higher amounts of M-protein in viro significantly. VLA-5+MPC-1+ myeloma cells attached to bone marrow stromal cells tightly, and their interaction was inhibited by the presence of anti-VLA-5 and MPC-1 antibody. Therefore, we could clarify the role of adhesion molecules such as VLA-5 and MPC-1 antigens on growth and differentiation of human myeloma cells: VLA-5-MPC-1- myeloma cells were proliferative immature cells and VLA-5+MPC-1+ mature myeloma cells might be derived from immature myeloma cells and attached to bone marrow stromal cells tightly.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] KAWANO M.M.: "Homotypic cell aggregations of human myeloma cells with ICAM-1 and LFA-1 molecules." British Journal of Haematology. 79. 583-588 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] SAKAI A.: "Interleukin-6 produced by renal-cell carcinoma cells and progression of multiple myeloma" New England Journal of Medicine. 324. 1893-1894 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 河野 道生: "IL-6とミエローマ" 臨床科学. 27. 1208-1214 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 田辺 修: "多発性骨髄腫とIL-6" 日本網内系学会会誌. 31. 437-446 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 親田 浩徳: "セルソーターによる前駆骨髄腫細胞の分離とその性状" Cytometry Research. 3(suppl.). 67-73 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HARADA H.: "Phenotypic difference of normal plasma cells from mature myeloma cells." Blood. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "Identification of immature and mature myeloma cells in the bone marrow of human myeloms." Blood. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 河野 道生: "形質細胞の増殖と腫瘍化" 臨床医. 18. 181-185 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 河野 道生: "形質細胞増殖性疾患とサイトカイン" 臨床血液. 33. 999-1011 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 原田 浩徳: "造血器腫瘍のオートクラインとパラクライン増殖" Oncologia. 25. 663-671 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 河野 道生: "多発性骨髄腫とサイトカイン" 現代医療. 25. 548-555 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 河野 道生: "サイトカインと疾病(編集:笠倉新平)分担" 日本医学館, 190 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "Homotypic cell aggregations of human myeloma cells with ICAM-1 and LFA-1 molecules." British Journal of Haematology. Vol.79. 583-588 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] SAKAI A.: "Interleukin-6 produced by renal-cell carcinoma cells and progression of multiple myeloma." New England Journal of Medicine. Vol.324. 1893-1894 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "IL-6 and myeloma." Journal of Clinical Science. Vol.27. 1208-1214 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] TANABE O.: "Multiple myeloma and intereleukin-6." Journal of Reticuloendothelial Systems. Vol.31. 437-446 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HARADA H.: "Separation of precursor myeloma cells by cell sorter and their characterization" Cytometry Research. Vol.3(Suppl.). 67-73 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HARADA H.: "Phenotypic difference of normal plasma cells from mature myeloma cells." Blood. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "Identification of immature and mature myeloma cells in the bone marrow of human myelomas." Blood. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "Growth and oncogenesis of plasma cells" Rinshoui. Vol.18. 181-185 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "Plasma cell proliferative disorders and cytokines" Clinical Hematology(Rinshoui). Vol.33. 999-1011 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HARADA H.: "Autocrine and paracrine growth in hematological malignancies." Oncologia. Vol.25. 663-671 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: "Multiple myeloma and cytokines." Gendai-Iryou. Vol.25. 548-555 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KAWANO M.M.: Cytokines and Diseases (Edited by Shinpei KASAKURA). Nihon Igakkan, 190 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 原田 浩徳: "セルソータによる前駆骨髄腫細胞の分離とその性状" Cytometry Research. 3(Suppl.). 67-73 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Harada.H.: "Phenotypic difference of normal plasma cells from mature myeloma cells." Blood. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawano M.M.: "Identification of immature and mature myeloma cells in the bone marrow of human myelomas." Blood. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 道生: "形質細胞の増殖と腫瘍化" 臨床医. 18. 181-185 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 道生: "形質細胞増殖性疾患とサイトカイン" 臨床血液. 33. 999-1011 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 原田 浩徳: "造血器腫瘍のオートクラインとパラクライン増殖" Oncologia. 25. 663-671 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 道生: "多発性骨髄腫とサイトカイン" 現代医療. 25. 548-555 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 河野 道生: "サイトカインと疾病(編集・笠倉新平)分担" 日本医学館, 190 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Michio M.KAWANO: "Homotypic aggregations of human myeloma cells with ICAMー1 and LFAー1 molecules." British Journal of Haematology. 79. 583-588 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 河野 道生: "ILー6とミエロ-マ" 臨床科学. 27. 1208-1214 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 河野 道生: "形質細胞の増殖と腫瘍化" 臨床医. 18. 181-185 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Michio M.KAWANO: "Differentiated expression of VLAー5 accounting for the heterogeneity of myeloma cells in human myelomas" Blood. (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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