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Analysis of the function of LR11 on normal leukocytes and leukemia cells

Research Project

Project/Area Number 23591368
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionChiba University

Principal Investigator

TAKEUCHI Masahiro  千葉大学, 医学部附属病院, 助教 (50466702)

Co-Investigator(Kenkyū-buntansha) OHWADA Chikako  千葉大学, 医学部附属病院, 助教 (80436352)
BUJO Hideaki  東邦大学, 医学部, 教授 (80291300)
NAKASEKO Chiaki  千葉大学, 大学院医学研究院, 准教授 (30323398)
Co-Investigator(Renkei-kenkyūsha) IWAMA Atsushi  千葉大学, 大学院医学研究院, 教授 (70244126)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords血液腫瘍学 / 白血病 / ニッチ / 低酸素 / 細胞接着
Research Abstract

We have identified and characterized a regulator of uPAR function, LR11 (also called SorLA or SORL1), in vascular smooth muscle cells (SMCs). Both LR11 mRNA and cell surface protein levels are elevated in immature leukemic cells, in turn leading to increased levels of sLR11 in acute leukemias. Thus, we analyzed the function of LR11 on normal hematopoietic cells and leukemia cells.
Results: K562 cells express very low levels of LR11 protein, but there was no difference in cell growth between mock transfected cells and LR11-overexpressing (LR11-ox) K562 cells in vitro. The percent of leukemia cells in PB of the mice transplanted with LR11-ox K562 cells on 4 weeks after transplantation were significantly higher than those of mice transplanted with mock cells. All the recipient mice transplanted with control U937 cells were died of leukemia by 3 weeks after transplantation, whereas the survival of mice transplanted with LR11-KD U937 cells were prolonged significantly.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (17 results)

All 2013 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (15 results)

  • [Journal Article] The soluble form of LR11 is a regulator of hypoxia-induced, uPAR-mediated adhesion of immature hematological cells2013

    • Author(s)
      Keigo Nishii, Chiaki Nakaseko, Meizi Jiang, Naomi Shimizu, Masahiro Takeuchi, Wolfgang Johann Schneider, and Hideaki Bujo
    • Journal Title

      J Biol Chem

      Volume: 288(17) Pages: 11877-86

    • Related Report
      2013 Final Research Report
  • [Journal Article] The soluble form of LR11 is a regulator of hypoxia-induced, uPAR-mediated adhesion of immature hematological cells2013

    • Author(s)
      Keigo Nishii, Chiaki Nakaseko, Meizi Jiang, Naomi Shimizu, Masahiro Takeuchi, Wolfgang Johann Schneider, and Hideaki Bujo
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288(17) Issue: 17 Pages: 11877-11886

    • DOI

      10.1074/jbc.m112.442491

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] LR11 plays critical roles in leukemogenesis of AML by regulating cell adhesion and homing ability2013

    • Author(s)
      西居圭吾、中世古知昭、武内正博、清水直美、大和田千佳子、塚本祥吉、川口岳晴、姜美子、岩間厚志、武城英明
    • Organizer
      第75回日本血液学会総会
    • Year and Date
      2013-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Serum soluble LR11 is a promising novel biomarker for B cell lymphoma2012

    • Author(s)
      川口岳晴、大和田千桂子、酒井紫緒、竹田勇輔、清水直美、武内正博、堺田恵美子、田久保耕平、海老沼宏幸、深町勇、東守洋、田丸淳一、横手幸太郎、武城英明、中世古知昭
    • Organizer
      53rd ASH annual meeting and exposition(米国血液学会年次総会)
    • Year and Date
      2012-12-10
    • Related Report
      2013 Final Research Report
  • [Presentation] LR11 Plays a Critical Role in Leukemogenesis of Acute Myeloid Leukemia by Regulating Adhesion and Homing Ability to Bone Marrow2012

    • Author(s)
      西居圭吾、武内正博、中世古知昭、武城英明ほか
    • Organizer
      54th ASH annual meeting and exposition(米国血液学会年次総会)
    • Year and Date
      2012-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] LR11 regulates the hypoxia-induced hematopoietic immature cell adhesion2012

    • Author(s)
      西居圭吾、武内正博、中世古知昭、武城英明ほか
    • Organizer
      第74回日本血液学会総会
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] LR11 regulates the hypoxia-induced hematopoietic immature cell adhesion.2012

    • Author(s)
      西居圭吾、武内正博、中世古知昭、武城英明 ほか
    • Organizer
      日本血液学会総会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2012 Research-status Report
  • [Presentation] Soluble LR11/SorLA, a Potential Circulating Marker Indicating the G-CSF-Induced Mobilization of Hematopoietic Stem Cells, Is a Modulator of G-CSF-Mediated Migration of HL-60 Cells2011

    • Author(s)
      清水直美、中世古知昭、武内正博、大和田千桂子、塚本祥吉、川口岳晴、西居桂吾、姜美子、横手幸太郎、深町勇、武城英明
    • Organizer
      53rd ASH annual meeting and exposition(米国血液学会年次総会)
    • Year and Date
      2011-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Serum soluble LR11 is a promising novel biomarker for malignant lymphoma2011

    • Author(s)
      川口岳晴、大和田千桂子、酒井紫緒、竹田勇輔、清水直美、武内正博、堺田恵美子、田久保耕平、海老沼宏幸、深町勇、東守洋、田丸淳一、横手幸太郎、武城英明、中世古知昭
    • Organizer
      第73回日本血液学会学術集会
    • Year and Date
      2011-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 可溶型LR11はCD87・CD11b複合体を介して単球系THP-1細胞を活性化する2011

    • Author(s)
      塚本祥吉、武内正博、杉田泰雅、山崎敦子、川口岳晴、酒井紫緒、竹田勇輔、大和田千桂子、清水直美、堺田恵美子、西居圭吾、姜美子、横手幸太郎、武城英明、中世古知昭
    • Organizer
      第73回日本血液学会学術集会
    • Year and Date
      2011-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 可溶性LR11は白血病細胞株HL-60の新たな走化性因子であり、G-CSFによる遊走能を増強する2011

    • Author(s)
      清水直美、中世古知昭、酒井紫緒、塚本祥吉、川口岳晴、竹田勇輔、大和田千桂子、武内正博、堺田恵美子、井関徹、西居桂吾、姜美子、横手幸太郎、武城英明
    • Organizer
      第73回日本血液学会学術集会
    • Year and Date
      2011-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Soluble LR11/SorLA, a Potential Circulating Marker Indicating the G-CSF-Induced Mobilization of Hematopoietic Stem Cells, Is a Modulator of G-CSF-Mediated Migration of HL-60 Cells2011

    • Author(s)
      清水直美、中世古知昭、武内正博、大和田千桂子、塚本祥吉、川口岳晴、西居桂吾、姜美子、横手幸太郎、深町勇、武城英明
    • Organizer
      53rd ASH annual meeting and exposition (米国血液学会年次総会)
    • Place of Presentation
      サンディエゴ
    • Related Report
      2011 Research-status Report
  • [Presentation] 可溶性LR11は白血病細胞株HL-60の新たな走化性因子であり、G-CSFによる遊 走能を増強する2011

    • Author(s)
      清水直美、中世古知昭、酒井紫緒、塚本祥吉、川口岳晴、竹田 勇輔、大和田千桂子、武内正博、堺田恵美子、井関徹、西居桂吾、姜美子、横手幸太郎、武城英明
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] 可溶型LR11はCD87・CD11b複合体を介して単球系THP-1細胞を活性化する2011

    • Author(s)
      塚本祥吉、武内正博、杉田泰雅、山崎敦子、川口岳晴、酒井紫緒、竹田勇輔、 大和田千桂子、清水直美、堺田恵美子、西居圭吾、姜美子、横手幸太郎、武城 英明、中世古知昭
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] Serum soluble LR11 is a promising novel biomarker for malignant lymphoma.2011

    • Author(s)
      川口岳晴、 大和田千桂子、酒井紫緒、竹田勇輔、清水直美、武内正博、堺田恵美子、田久保耕平、海老沼宏幸、深町勇、東守洋、田丸淳一、横手幸太郎、武城 英明、中世古知昭
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] Serum soluble LR11 is a promising novel biomarker for B cell lymphoma.2011

    • Author(s)
      川口岳晴、 大和田千桂子、酒井紫緒、竹田勇輔、清水直美、武内正博、堺田恵美子、田久保耕平、海老沼宏幸、深町勇、東守洋、田丸淳一、横手幸太郎、武城 英明、中世古知昭
    • Organizer
      53rd ASH annual meeting and exposition (米国血液学会年次総会)
    • Place of Presentation
      サンディエゴ
    • Related Report
      2011 Research-status Report
  • [Presentation] LR11 plays a critical role in leukemogenesis of AML by regulating cell adhes ion and homing ability

    • Author(s)
      西居桂吾、中世古知昭、武内正博、清水直美、大和田千桂子、塚本祥吉、川口岳晴、姜美子、岩間厚志 、武城英明
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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