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Study on regulatory mechanism of hematopoiesis by RCAS-1 ; Application in hematopoietic stem cell transplantation.

Research Project

Project/Area Number 14570987
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MUTA Koichiro  Kyushu University, Hospital, Assistant Professor, 大学病院, 講師 (50229928)

Co-Investigator(Kenkyū-buntansha) ABE Yasunobu  Kyushu University, Hospital, Research Associate, 大学病院, 助手 (90304774)
中島 学  九州大学, 生体防御医学研究所, 助手 (50198074)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsRCAS1 / macrophages / erythroid / progenitors / apoptosis / サラセミア / apoptosis / hematopoiesis / macrophage
Research Abstract

Novel human tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells) has been shown to induce apoptosis in normal human erythroid progenitor cells, which express putative RCAS1 receptors. In the present study, we investigated a possible role of RCAS1 produced by human peripheral blood monocytes (CD14 positive cells) and monocyte-derived macrophages. RCAS1 was immunohistochemically detected in cytoplasm of monocytes as well as macrophages. When macrophages were stimulated with LPS, the expression of RCAS1 was remarkably enhanced not only in the cytoplasm but also on the cell membrane. An increased production of RCAS1 mRNA was observed in LPS-stimulated macrophages by quantitative RT-PCR analysis. The soluble RCAS1 molecules were also detected in the culture supernatants obtained from LPS-stimulated macrophages, but not from unstimulated cells. LPS-stimulated macrophages induced cell death of erythroid progenitor cells. This cytotoxic effect was abolished by addition of 22-1-1 monoclonal antibody. These results suggested that macrophages may negatively regulate erythropoiesis through induction of cell death caused in part by RCAS1 molecules. The present findings might also be related to the in-vitro expansion of hematopoietic stem and progenitor cells for transplantation.

Report

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

    (34 results)

All 2006 2005 2004 2003 Other

All Journal Article (22 results) Publications (12 results)

  • [Journal Article] Hydroxyurea responses and fetal hemoglobin induction in beta-thalassemia/HbE patients' peripheral blood erythroid cell culture.2006

    • Author(s)
      Watanapokasin R et al.
    • Journal Title

      Ann Hematol. 85

      Pages: 164-169

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hydroxyurea responses and fetal hemoglobin induction in beta-thalassemia/HbE patients' peripheral blood erythroid cell culture.2006

    • Author(s)
      Watanapokasin R et al.
    • Journal Title

      Ann Hematol 85

      Pages: 164-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pivotal role of peroxisome proliferator-activated receptor gamma (PPARgamma) in regulation of erythroid progenitor cell proliferation and differentiation.2005

    • Author(s)
      Nagasawa E et al.
    • Journal Title

      Exp Hematol. 33

      Pages: 857-864

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel mechanism in suppression of erythropoiesis during inflammation : a crucial role of RCAS1.2005

    • Author(s)
      Suehiro Y et al.
    • Journal Title

      Eur J Haematol. 74

      Pages: 365-373

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of NF-kappa B in regulation of apoptosis of erythroid progenitor cells.2005

    • Author(s)
      Sae-Ung N et al.
    • Journal Title

      Eur J Haematol. 74

      Pages: 315-323

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via a Bc1-2 independent pathway.2005

    • Author(s)
      Zhang M et al.
    • Journal Title

      Leuk Lymphoma. 46

      Pages: 425-433

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pivotal role of peroxisome proliferator-activated receptor gamma (PPARgamma) in regulation of erythroid progenitor cell proliferation and differentiation.2005

    • Author(s)
      Nagasawa E et al.
    • Journal Title

      Exp Hematol 33

      Pages: 857-864

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel mechanism in suppression of erythropoiesis during inflammation : a crucial role of RCAS1.2005

    • Author(s)
      Suehiro Y et al.
    • Journal Title

      Eur J Haematol 74

      Pages: 365-373

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of NF-kappa B in regulation of apoptosis of erythroid progenitor cells.2005

    • Author(s)
      Sae-Ung N et al.
    • Journal Title

      Eur J Haematol 74

      Pages: 315-323

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via a Bcl-2 independent pathway.2005

    • Author(s)
      Zhang M et al.
    • Journal Title

      Leuk Lymphoma 46

      Pages: 425-433

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Role of NF-kB in Regulation of Apoptosis of Erythroid Progenitor Cells2005

    • Author(s)
      Sae-ung N et al.
    • Journal Title

      Eur J Haematol (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of Macrophages in Regulation of Apoptosis of Human Erythroid Progenitor Cells2005

    • Author(s)
      Youko Suehiro et al.
    • Journal Title

      Eur J Haematol (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Selective cyclooxygenase 2 inhibitor NS-398 induces apoptosis in myeloma cells via Bcl-2 independent pathway2005

    • Author(s)
      Min Zhang et al.
    • Journal Title

      Leukemia and Lymphoma (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of human tumor-associated antigen RCAS1 in adult T-cell leukemia/lymphoma.2004

    • Author(s)
      Muta K et al.
    • Journal Title

      Int J Hematol. 79

      Pages: 340-344

    • NAID

      10013082056

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of human tumor-associated antigen RCAS1 in adult T-cell leukemia/lymphoma.2004

    • Author(s)
      Muta K et al.
    • Journal Title

      Int J Hematol 79

      Pages: 340-344

    • NAID

      10013082056

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The signaling pathways of erythropoietin and interferon-gamma differ in preventing the apoptosis of mature erythroid progenitor cells2004

    • Author(s)
      Paiboonsukwong K et al.
    • Journal Title

      Int J Hmatol 78

      Pages: 421-428

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The signaling pathways of erythropoietin and interferon-gamma differ in preventing the apoptosis of mature erythroid progenitor cells.2003

    • Author(s)
      Paiboonsukwong K et al.
    • Journal Title

      Int J Hematol. 78

      Pages: 421-428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis.2003

    • Author(s)
      Abe Y et al.
    • Journal Title

      Int J Hematol. 77

      Pages: 359-363

    • NAID

      50000835828

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p16(INK4a) induces differentiation and apoptosis in erythroid lineage cells.2003

    • Author(s)
      Minami R et al.
    • Journal Title

      Exp Hematol. 31

      Pages: 355-362

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The signaling pathways of erythropoietin and interferon-gamma differ in preventing the apoptosis of mature erythroid progenitor cells.2003

    • Author(s)
      Paiboonsukwong K et al.
    • Journal Title

      Int J Hematol 78

      Pages: 421-428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis.2003

    • Author(s)
      Abe Y et al.
    • Journal Title

      Int J Hematol 77

      Pages: 359-363

    • NAID

      50000835828

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p16(INK4a) induces differentiation and apoptosis in erythroid lineage cells.2003

    • Author(s)
      Minami R et al.
    • Journal Title

      Exp Hematol 31

      Pages: 355-362

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Abe Y, Oshima K, Nakashima M et al.: "Expression of apoptosis-associated protein RCAS1 in macrophage of histiocytic necrotizing lymphadenitis"International Journal of Hematology. 77. 359-363 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Muta K, Oshima K, Abe Y et al.: "Expression of human tumor-associated antigen RCAS1 in adult T-cell leukemia/lymphoma"International Journal of Hematology. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Minami R, Muta K, Umemura T et al.: "p16(INK4a) induces differentiation and apoptosis in erythroid lineage cells"American Journal of Hematology. 31. 355-362 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sonoda K, Miyamoto S, Hirakawa T et al.: "Associated between RCAS1 expression and clinical outcome in uterine endometrial cancer"British Journal of cancer. 89. 546-551 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okada K, Nakashima M, Komuta K et al.: "Expression of tumor-associated membrane antigen, RCAS1, in human colorectal carcimomas and possible role in apoptosis of tumor-infiltrating lymp"Modern Pathology. 16. 679-685 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe H, Enjoji M, Nakashima M et al.: "Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma"Journal of Hepathology. 39. 559-563 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suehiro Y, Muta K et al.: "Involvement of macrophages in induction of apoptosis of human erythroid progenitor cells"Blood. 100・1. 306a (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe T, Ohshinma K et al.: "Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis"International Journal of Hematology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akashi T, Oimomi H, Nishiyama K, Nakashima M et al.: "Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1 in pancreatic cancer"Pancreas. 26. 49-55 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oizumi S, Yamazaki K, Nakashima M et al.: "RCAS1 expression : a potential prognostic marker for adenocarcinomas of the lung"Oncology. 62. 333-339 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enjoji M, Nakashima M et al.: "The tumor-associated antigen, RCAS1, can be expressed in immune-mediated diseases as well as in carcinomas of biliary tract"Journal of Hepatology. 36. 786-792 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enjoji M, Nakamuta M, Noguchi K, Sugimoto R, Kotoh K, Nawata H, Nakashima M, Watanabe T: "RCAS1 expression in immune-mediated liver diseases"Journal of Clinical Gastroenterology. 34. 286-287 (2002)

    • Related Report
      2002 Annual Research Report

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

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