The role of megakaryocytic lineage cells in leukemia/lymphoma cell proliferation

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591113
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: HATTORI Koichi The University of Tokyo, 医科学研究所, 特任准教授 (10360116)
• Project Period (FY): 2008 – 2010
• Keywords: 癌 / 酵素 / 細胞・組織 / 生体分子 / 凝固・線溶

Research Abstract

The main fibrinolytic enzyme, plasmin, can activate matrix metalloproteinases (MMPs) which has been linked to various malignancies. Here we provide the evidence that blockade of Plg reduces leukemia-lymphoma growth by inhibiting MMP activity. The data presented in this study demonstrate a previously undescribed role of plasmin in lymphoproliferative disorders and provide strong evidence that specific blockade of Plg represents a promising approach for the regulation of leukemia-lymphoma growth.

Research Products

• [Journal Article] Tumor necrosis receptor-associated factor (Traf)2 controls homeostasis of the colon to prevent spontaneous development of murine inflammatory bowel disease, (2011)
  • Author(s): Piao JH, Hasegawa M, Heissig B, Hattori K, Takeda K, Iwakura Y, Okumura K, Inohara N, Nakano H
  • Journal Title: J Biol Chem (in press)
  • Peer Reviewed
• [Journal Article] 血液線維素溶解系因子による骨髄細胞の動態制御 中外医学社Annual Review (2011)
  • Author(s): 服部浩一、西田知恵美
  • Journal Title: 血液 Pages: 187-195
• [Journal Article] Tissue type plasminogen activator regulates myeloid-cell (2010)
  • Author(s): Ohki M, Ohki Y, Ishihara M, Rosenkvist J, Gritli I, Tashiro Y, Akiyama H, Komiyama H, Lund LR, Nitta A, Yamada K, Zhu Z, Ogawa H, Yagita H, Okumura K, Nakauchi H, Werb Z, Heissig B, Hattori K
  • Journal Title: dependent neoangiogenesis during tissue regeneration Blood 115 Pages: 4302-4312
  • Peer Reviewed
• [Journal Article] Role of Neutrophil-derived matrix metalloproteinase-9 for tissue regeneration. (2010)
  • Author(s): Heissig B, Nishida C, Tashiro Y, Sato Y, Ishihara M, Ohki M, Hattori K
  • Journal Title: Histology & Histopathology 25 Pages: 765-770
  • Peer Reviewed
• [Journal Article] Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and inVitro. (2010)
  • Author(s): Aoki N., Yokoyama R., Asai N., Ohki M., Ohki Y., Kusubata K., Heissig B., Hattori K., Nakagawa Y., Matsuda T.
  • Journal Title: Endocrinology 151 Pages: 2567-2576
  • Peer Reviewed
• [Journal Article] 骨髄異形成と造血微小環境の異常 Dysfuction of bone marrow microenvironment in myelodysplasia (2010)
  • Author(s): 服部浩一、佐藤亜紀
  • Journal Title: 血液・腫瘍科 科学評論社 61 Pages: 660-666
• [Journal Article] 線維素溶解系による造血幹細胞ニッチの制御機構 (2010)
  • Author(s): 服部浩一,西田知恵美
  • Journal Title: 日本血栓止血学会雑誌 21 Pages: 27-31
• [Journal Article] 造血幹細胞ニッチにおけるMMP-9の役割 (2010)
  • Author(s): 服部浩一、田代良彦
  • Journal Title: 生化学 第82巻第10号 Pages: 979-984
• [Journal Article] Targeted deletion of matrix metalloproteinase-9 reduces neutrophil accumulation during G-CSF-induced neoangiogenesis. (2009)
  • Author(s): Sato Y, Ohki Y, Akiyama H, Rosenkvist J, Gritli I, Okumura K, Ogawa H, Heissig B, Hattori K, Ohsaka A
  • Journal Title: ytometry Res 19 Pages: 53-62
  • Peer Reviewed
• [Journal Article] Metalloproteinase regulation improves in vitro generation of efficacious platelets from embryonic stem cells. (2008)
  • Author(s): Nishikii H, Eto K, Tamura N, Hattori K, Heissig B, Kanaji T, Sawaguchi A, Goto S, Ware J, Nakauchi H
  • Journal Title: J Exp Med 205 Pages: 1917-1927
  • Peer Reviewed
• [Presentation] 生体内細胞分化制御因子としてのMT1-MMPの機能解析 (2011)
  • Author(s): 西田知恵美、楠畑かおり、田代良彦、清木元治,中内啓光、Heissig Beate、服部浩一
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 京王プラザホテル.東京
  • Year and Date: 20110301-20110302
• [Presentation] 線維素溶解系の活性化による骨髄内間葉系幹細胞の増殖 (2011)
  • Author(s): 楠畑かおり、小泉摩希子、HeissigBeate、服部浩一
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 京王プラザホテル.東京
  • Year and Date: 20110301-20110302
• [Presentation] 線溶系因子プラスミンによる赤血球造血制御機構の解明 (2011)
  • Author(s): Yurai Okaji, Chiemi Nishida, Koichi Hattori, Beate Heissig
  • Organizer: ワークショップ「個体レベルのがん研究の魅力:培養細胞と臨床研究をつなぐマトリクス」
  • Place of Presentation: 琵琶湖ホテル.大津
  • Year and Date: 20110203-20110204
• [Presentation] MT1-MMP plays a critical role in the cell growth and maturation. (2011)
  • Author(s): Chiemi Nishida, Kaori Kusubata, Motoharu Seiki, Hiromitsu Nakauchi, Koichi Hattori, Beate Heissig
  • Organizer: ワークショップ「個体レベルのがん研究の魅力:培養細胞と臨床研究をつなぐマトリクス」
  • Place of Presentation: 琵琶湖ホテル.大津
  • Year and Date: 20110203-20110204
• [Presentation] KoichiHattori MT1-MMP Plays a Critical Role In the Modulation of Hematopoiesis (2010)
  • Author(s): Nishida Chiemi, Heissig Beate, Tashiro Yoshihiko, Seiki Motoharu, Hiromithu Nakauchi
  • Organizer: 52nd ASH Annual Meeting ; Orange County Convention Center
  • Place of Presentation: Orlando, FL
  • Year and Date: 20101204-20101207
• [Presentation] Plasminogen Deficiency Impairs Erythropoietic Recovery Capacity in Male C57BL/6J Mice through Testosterone Defect. (2010)
  • Author(s): Okaji Yurai, Nishida Chiemi, Gritli Ismael, Tashiro Yoshihiko, Ohki Makiko, Hattori Koichi, Heissig Beate
  • Organizer: 52nd ASH Annual Meeting ; Orange County Convention Center
  • Place of Presentation: Orlando, FL
  • Year and Date: 20101204-20101207
• [Presentation] 服部浩一 MT1-MMP is a critical modulator of normal hematopoiesis. (2010)
  • Author(s): Chiemi Nishida, Heissig, Motoharu Seiki, Hiromitsu Nakauchi
  • Organizer: 第72回日本血液学会
  • Place of Presentation: パシフィコ横浜.横浜
  • Year and Date: 20100924-20100926
• [Presentation] リンパ腫増殖における線維素溶解系の役割と新規治療法の開発 (2010)
  • Author(s): 石原誠人、ベアテハイジッヒ、田代良彦、西田知恵美、小泉摩希子、和中敬子、津田裕子、岡田芳男、八木田秀雄、奥村康、中内啓光、服部浩一
  • Organizer: 第72回日本血液学会
  • Place of Presentation: パシフィコ横浜.横浜
  • Year and Date: 20100924-20100926
• [Presentation] 生体内組織再生における線溶系因子PAI-1の機能解明 (2010)
  • Author(s): 田代良彦、石原誠人、西田知恵美、Ismail Gritli1)、小泉摩季子、小見山博光、坂本一博、Beate Heissig、宮田敏男、中内啓光、服部浩一
  • Organizer: 第72回 日本血液学会
  • Place of Presentation: パシフィコ横浜.横浜
  • Year and Date: 20100924-20100926
• [Presentation] Epidermal growth factor-like domain 7, a vascular niche factor, regulates myelopoiesis. (2010)
  • Author(s): Ismael Gritli, Chiemi Nishida, Makoto Ishihara, Hiromitsu Nakauchi, Koichi Hattori, Beate Heissig.
  • Organizer: The 72nd Annual Meeting of the Japanese Society of Hematology.
  • Place of Presentation: Pacifico Yokohama
  • Year and Date: 2010-09-24
• [Presentation] 癌増殖における線維素溶解系因子の役割と新規治療法の開発 (2010)
  • Author(s): 石原誠人、山本玲、八木田秀雄、奥村康、ハイジッヒベアテ、服部浩一
  • Organizer: 第69回日本癌学会学術集会
  • Place of Presentation: 大阪国際会議場.大阪
  • Year and Date: 2010-09-24
• [Presentation] 癌間質・微小環境形成における骨髄由来細胞動員の意義 (2010)
  • Author(s): 服部浩一
  • Organizer: 第51回日本臨床細胞学会指名講演
  • Place of Presentation: パシフィコ横浜 横浜
  • Year and Date: 2010-05-31
• [Presentation] Contribution of the fibrinolytic system to hematopoiesis and angiogenesis during tissue regeneration. (2010)
  • Author(s): 服部浩一
  • Organizer: 第33回日本血栓止血学会学術集会招待講演
  • Place of Presentation: 城山観光ホテル.鹿児島
  • Year and Date: 2010-04-20
• [Presentation] プロテアーゼ活性化を起点とした癌と骨髄とのクロストーク. (2009)
  • Author(s): 服部浩一
  • Organizer: 第12回癌と骨病変研究会招待講演
  • Place of Presentation: 大阪・千里
  • Year and Date: 2009-11-20
• [Presentation] The Role of fibrinolytic system in lymphoma progression ; implication for targets. (2009)
  • Author(s): Ishihara M, Heissig B, Tashiro Y, Tsuda Y, Wanaka K, Okada Y, Hattori K
  • Organizer: The 71^<st> Annual Meeting of the Japanese Society of Hematology 2009 : Kyoto(第71回日本血液学会総会ワークショップ発表)
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] tPA regulates bone marrow derived cell dependent neoangiogenesis during tissue regeneration. (2009)
  • Author(s): Hattori K, Ohki M, Ohki Y, Nishida C, Ishihara M, Tashiro Y, Gritli I, Nakauchi H, Heissig B
  • Organizer: The 71^<st> Annual Meeting of the Japanese Society of Hematology(第71回日本血液学会総会プレナリーセッション発表)
  • Place of Presentation: Kyoto
  • Year and Date: 2009-10-23
• [Presentation] 生体内造血制御機構におけるMT1-MMPの機能解析 (2009)
  • Author(s): 西田知恵美,Heissig Beate,清木元治,中内啓光,服部浩一
  • Organizer: 第71回日本血液学会総会発表
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] 癌微小環境形成における骨髄由来細胞の動員機構 (2009)
  • Author(s): 服部浩一,石原誠人,Heissig B
  • Organizer: 第10回運動器科学研究会招待講演
  • Place of Presentation: 東京
  • Year and Date: 2009-09-18
• [Presentation] Fibrinolytic system plays a key role in tumor growth and apoptosis. (2009)
  • Author(s): Resenkvist J, Ishihara M, Ismael Gritli, Nishida C, Heissig Beate、Hattori K
  • Organizer: 平成21年度医科学研究所研究成果発表会
  • Place of Presentation: Tokyo
  • Year and Date: 2009-06-01
• [Presentation] 生体内造血制御機構におけるMT1-MMPの重要性 (2009)
  • Author(s): 西田知恵美,新谷大悟,清木元治,Heissig Beate,服部浩一
  • Organizer: 第8回日本再生医療学会総会口演
  • Place of Presentation: 東京
  • Year and Date: 2009-03-05
• [Presentation] 末梢血幹細胞動員における線溶系因子の機能解析 (2009)
  • Author(s): 大木摩希子,大木勇一,秋山晴代,Heissig Beate,服部浩一
  • Organizer: 第8回日本再生医療学会総会発表
  • Place of Presentation: 東京
  • Year and Date: 2009-03-05
• [Presentation] 血液線維素溶解系と骨髄細胞動態との相関 (2008)
  • Author(s): 服部浩一
  • Organizer: 第14回血液科学セミナー招待講演
  • Place of Presentation: 東京
  • Year and Date: 20080000
• [Presentation] 骨髄由来細胞動員を介した組織再生制御機構 (2008)
  • Author(s): 服部浩一
  • Organizer: 第59回日本電気泳動学会シンポジウム指名講演
  • Place of Presentation: 神奈川
  • Year and Date: 2008-11-15
• [Presentation] 骨髄由来細胞によるがん関連ニッチ形成機構 (2008)
  • Author(s): 服部浩一
  • Organizer: 第26回日本骨代謝学会学術集会ミニシンポジウム指名講演
  • Place of Presentation: 大阪
  • Year and Date: 2008-10-30
• [Presentation] 骨髄由来細胞動員による腫瘍血管新生制御機構 (2008)
  • Author(s): 服部浩一
  • Organizer: 第67回日本癌学会学術総会指名講演
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 生体内造血制御機構におけるMT1-MMPの重要性 (2008)
  • Author(s): 西田知恵美、新谷大悟、清木元治、Heissig Beate、服部浩一
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] 癌増殖における線維素溶解系因子の役割と新規治療法の開発 (2008)
  • Author(s): 石原誠人、Heissig Beate、服部浩一
  • Organizer: 第70回日本血液学会総会・優秀ポスター賞
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] Fibrinolytic system regulates myeloid-cell dependent neoangiogenesis during tissue regeneration.
  • Author(s): 服部浩一
  • Organizer: 3^<rd> Symposium of IMSUT & RCAST Global COE on New Horizon of Stem Cell Biology and Immunotherapy
  • Place of Presentation: 東京大学医科学研究所 東京都
• [Remarks] ホームページ等
  • URL: http://stemcell-u-tokyo.org/sc-re/