The coagulation and the fibrinolytic system are essential drivers in the pathogenesis of leukemia and lymphoma
Project/Area Number |
23591371
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | The University of Tokyo |
Principal Investigator |
HATTORI Koichi 東京大学, 医科学研究所, 特任准教授 (10360116)
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Project Period (FY) |
2011 – 2013
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Project Status |
Completed (Fiscal Year 2013)
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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 | 血液内科学 / 癌 / 酵素 / 生体分子 / 生理活性 / 発生・分化 / プラスミン / マトリックスメタロプロテイナーゼ / 血管新生 / 細胞外ドメイン分泌 / 造血因子 / HIF-1 / PAI-1 / 細胞外微小環境 |
Research Abstract |
The main coagulation and fibrinolytic factor plasmin, which is derived from its proform plasminogen (Plg) and one of its downstream targets, matrixmetalloproteinases (MMP), have been linked to various malignancies. Here, we provide the evidence that blockade of plasmin reduces lymphoma growth by inhibiting MMP-dependent recruitment of bone marrow derived CD11b+ cells locally within the lymphoma tissue. Genetic Plg deficiency and drug-mediated plasmin blockade delayed lymphoma growth and diminished MMP dependent marrow derived CD11b+ cell infiltration into lymphoma tissues and formation of malignant niche. We could show that CD11b+ cells play key a role in the growth of lymphoma and the other malignancies through malignant niche formation. Collectively, our data demonstrate a previously undescribed role of fibrinolytic system in tumor growth and provide strong evidence that specific blockade of plasmin a promising approach for the cancer treatments.
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Report
(4 results)
Research Products
(85 results)
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[Journal Article] Bonemarrow-derived CD11b+Jagged-2+ cells promote epithelial to mesenchymal transition and metastization in colorectal cancer.2013
Author(s)
Caiado F, Carvalho T, Rosa I, Remedio L, Costa A, Matos J, Heissig B, Yagita H, Hattori K, da Silva JP, Fidalgo P, Dias Pereira A, Dias S.
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Journal Title
Cancer Res.
Volume: 73
Issue: 14
Pages: 4233-46
DOI
Related Report
Peer Reviewed
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[Journal Article] MT1-MMP plays a critical role in henatopoiesis by regulating HIF-mediated chemo-/cytokine gene transcription within niche cells.2012
Author(s)
Chiemi Nishida, Kaori Kusubata, Yoshihiko Tashiro, Ismael Gritli, Aki Sato, Makiko Ohki-Koizumi, Yohei Morita, Makoto Nagano, Takeharu Sakamoto, Naohiko Koshikawa, Takahiro Kuchimaru, Shinae Kizaka-Kondoh, Motoharu Seiki, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
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Journal Title
Blood
Volume: 119
Issue: 23
Pages: 5404-5416
DOI
Related Report
Peer Reviewed
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[Journal Article] Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice2012
Author(s)
Yoshihiko Tashiro, Chiemi Nishida, Kaori Sato-Kusubata, Makiko Ohki-Koizumi, Makoto Ishihara, Aki Sato, Ismael Gritli, Hiromitsu Komiyama, Yayoi Sato, Takashi Dan, Toshio Miyata, Ko Okumura, Yuichi Tomiki, Kazuhiro Sakamoto, Hiromitsu Nakauchi, Beate Heissig, and Koichi Hattori.
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Journal Title
Blood
Volume: 119
Issue: 26
Pages: 6382-6393
DOI
Related Report
Peer Reviewed
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[Journal Article] Plasmin inhibitor reduces lymphoid tumor growth by suppressing matrixmetallproteinase-9 dependent CD11b+/F4/80+ myeloid cell recruitment2012
Author(s)
Ishihara M, Heissig B, Nishida C, Rosenkvist J, Tashiro Y, Ohki M, Wanaka K, Tsuda Y, Okada Y, Nakauchi H, Hattori K
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Journal Title
Leukemia
Volume: 26
Issue: 2
Pages: 332-339
DOI
Related Report
Peer Reviewed
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[Presentation] PAI-1阻害剤による血管新生及び組織再生促進療法2013
Author(s)
宗像慎也,田代良彦,島津浩,西田知恵美,イスマエルグリツリ,佐藤亜紀,小泉摩季子,楠畑かおり,小見山博光,坂本一博,宮田敏男,ハイジッヒベアテ,服部浩一
Organizer
第113回日本外科学会定期学術集会
Place of Presentation
福岡
Year and Date
2013-04-11
Related Report
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[Presentation] 造血微小環境におけるMT1-MMPと造血因子の発現調節2013
Author(s)
西田知恵美,楠畑かおり,田代良彦, Gritli, I佐藤亜紀,小泉(大木)摩季子,守田陽平,長野真,坂本毅治,口丸高弘.近藤科江,清木元治,中内啓光, Heissig B,服部浩一
Organizer
第12回日本再生医療学会
Place of Presentation
パシフィコ横浜、横浜市
Year and Date
2013-03-22
Related Report
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[Presentation] PAI-1阻害剤による血管新生及び組織再生促進療法2013
Author(s)
田代良彦,宗像慎也,西田知恵美,石原誠人,Gritli I,島津浩,佐藤亜紀,楠畑かおり,小泉摩季子,小見山博光,坂本一博,宮田敏夫,中内啓光,Heissig B,服部浩一
Organizer
第12回日本再生医療学会総会
Place of Presentation
横浜
Year and Date
2013-03-22
Related Report
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[Presentation] PAI-1阻害剤による血管新生及び組織再生促進療法2013
Author(s)
宗像慎也, 田代良彦,島津浩,西田知恵美,イスマエルグリツリ,佐藤亜紀,小泉摩季子,楠畑かおり,小見山博光,坂本一博,宮田敏男,ハイジッヒベアテ,服部浩一
Organizer
第113回日本外科学会定期学術集会
Place of Presentation
福岡国際会議場 福岡市
Related Report
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[Presentation] MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemo-/cytokine gene transcription within niche cells2012
Author(s)
Nishida C, Sato-Kusubata K, Tashiro Y, Gritli I, Sato A, Ohki-Koizumi M, Morita Y, Nagano M, Sakamoto T, Seiki M, Nakauchi H, Heissig B, Hattori K
Organizer
第54回アメリカ血液学会
Place of Presentation
Georgia World Congress Center Atlanta
Year and Date
2012-12-09
Related Report
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[Presentation] MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated cytokine gene transcription2012
Author(s)
NishidaC, Sato-Kusubata K, TashiroY, Gritli I, Sato A, Ohki-Koizumi M, Morita Y, Nagano M ,Sakamoto T, Seiki M, Nakauchi H, Heissig, B Hattori K
Organizer
第74回日本血液学会
Place of Presentation
京都国際会館、京都市
Year and Date
2012-10-20
Related Report
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[Presentation] Aplasmin inhibitor prevents cytokine mediated inflammatory disease2012
Author(s)
Sato, A, Nishida C, Gritli I,Sato-Kusubata K, Yagita H, Okumura K, Tsuda Y,Okada Y , Takahashi S, Tojo A, Nakauchi H, Heissig B, Hattori K
Organizer
第74回日本血液学会
Place of Presentation
京都国際会館、京都市
Year and Date
2012-10-20
Related Report
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[Presentation] MT1-MMP REGULATES HEMATOPOIESIS THROUGH HIF-MEDIATED CHEMO-/CYTOKINE RELEASE FROM THE BONE MARROW NICHE2012
Author(s)
Nishida C, Sato-Kusubata K, Tashiro Y, Gritli I, Sato A, Ohki-Koizumi M, Morita Y, Nagano M, Sakamoto T, Seiki M, Nakauchi H, Heissig B, Hattori K
Organizer
第12回東京大学生命科学シンポジウム
Place of Presentation
東大(ポスター)
Year and Date
2012-06-30
Related Report
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[Presentation] MT1-MMP REGULATES HEMATOPOIESIS THROUGH HIF-MEDIATED CHEMO-/CYTOKINE RELEASE FROM THE BONE MARROW NICHE2012
Author(s)
Nishida C, Sato-Kusubata K, Tashiro Y, Gritli I, Sato A, Ohki-Koizumi M, Morita, Y, Nagano M, Sakamoto T,Seiki M, Nakauchi H, Heissig B, Hattori K
Organizer
第10回国際幹細胞学会
Place of Presentation
パシフィコ横浜、横浜市(ポスター)
Year and Date
2012-06-16
Related Report
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