2013 Fiscal Year Final Research Report
Molecular and cellular effects of tumor microenvironment-specific Galectin-3 in leukemia
| Project/Area Number |
23591403
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
KURODA Junya 京都府立医科大学, 医学(系)研究科(研究院), 講師 (70433258)
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| Project Period (FY) |
2011 – 2013
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| Keywords | ガレクチン-3 / 慢性骨髄性白血病 / 骨髄腫瘍環境 / 分子標的 |
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| Research Abstract |
We in this study investigated the molecular and biologic effects of galectin-3 (Gal-3) which is specifically induced by tumor-microenvironment in leukemic cells of chronic myelogenous leukemia (CML). Gal-3 promoted cell proliferation of leukemic cells via the activation of ERK and AKT as well as the inhibition of extracellular SERPINA1-albumin complex. Gal-3 also induced the expression of anti-apoptotic MCL-1 and caused the resistance to molecular targeted agents and genotoxic agents in CML cells. Interestingly, Gal-3 expression promoted the lodgment of leukemic cells in bone marrow in vivo. Finally, our study revealed that the combinatory use of protein phosphatase-2 activator in addition to the currently utilized molecular targeted agents, such as imatinib or dasatinib, was effective in overcoming those series of leukemia-promoting effects of Gal-3,
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Research Products
(16 results)
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[Journal Article] Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression leads to paracrine growth promotion of chronic myelogenous leukemic cells2014
Author(s)
Nakayama R, Kuroda J, Taniyama N, Yamamoto-Sugitani M, Wada S, Kiyota M, Mizutani S, Chinen Y, Matsumoto Y, Nagoshi H, Shimura Y, Kobayashi T, Horiike S, Taniwaki M
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Journal Title
Leukemia Res
Volume: 38
Pages: 103-108
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[Journal Article] FTY720 induces apoptosis of chronic myelogenous leukemia cells via dual activation of BIM and BID and overcomes various types of resistance to tyrosine kinase inhibitors2013
Author(s)
Kiyota M, Kuroda J, Yamamoto-Sugitani M, Shimura Y, Nakayama R, Nagoshi H, Mizutani S, Chinen Y, Sasaki N, Sakamoto N, Kobayashi T, Matsumoto Y, Horiike S, Taniwaki M
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Journal Title
Apoptosis
Volume: 18
Pages: 1437-46
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[Journal Article] Galectin-3 induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia2011
Author(s)
Yamamoto-Sugitani M, Kuroda J, Ashihara E, Nagoshi H, Kobayashi T, Matsumoto Y, Sasaki N, Shimura Y, Kiyota M, Nakayama R, Akaji K, Taki T, Uoshima N, Kobayashi Y, Horiike S, Maekawa T, Taniwaki M
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Journal Title
Proc Natl Acad Sci USA
Volume: 108
Pages: 17468-17473
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[Presentation] Fingolimod (FTY720) Overcomes the Resistance to Tyrosine Kinase Inhibitors Via Dual Activation of BIM and BID in Chronic Myelogenous Leukemia The American Society of Hematology2012
Author(s)
Kiyota M, Kuroda J, Yamamoto-Sugitani M, Shimura Y, Nakayama R, Nagoshi H, Mizutani S, Chinen Y, Sakamoto N, Kobayashi T, Matsumoto Y, Horiike S, Taki T, Taniwaki M
Organizer
54th Annual Meeting and Exposition
Year and Date
20121208-10
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[Presentation] Galectin-3 protects CML leukemic cells by antagonizing SERPINA1-albumin complex2012
Author(s)
Nakayama R, Kuroda J, Taniyama N, Wada S, Sugitani M, Shimura Y, Nagoshi H, Mizutani S, Chinen Y, Sakamoto N, Kobayashi T, Matsumoto Y, Horiike S, Sato K, Taniwaki M
Organizer
第74回日本血液学会学術集会
Year and Date
20121019-21
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[Presentation] FTY720 induces apoptosis via both Bim-mediated intrinsic and extrinsic pathway in CML2012
Author(s)
Kiyota M, Kuroda J, Yamamoto-Sugitani M, Shimura Y, Nakayama R, Nagoshi H, Mizutani S, Chinen Y, Sakamoto N, Kobayashi T, Matsumoto Y, Horiike S, Taniwaki M
Organizer
第74回日本血液学会学術集会
Year and Date
20121019-21
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[Presentation] Leukemia microenvironment-specific galectin-3 expression promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia2012
Author(s)
Yamamoto-Sugitani M, Kuroda J, Ashihara E, Nagoshi H, Kobayashi T, Matsumoto Y, Sasaki N, Shimura Y, Kiyota M, Nakayama R, Akaji K, Taki T, Uoshima N, Kobayashi Y, Horiike S, Maekawa T, Taniwaki M
Organizer
The 3^<rd> JSH International Symposium 2012
Year and Date
20120526-27
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[Presentation] Leukemia Microenvironment-Specific Galectin-3 Expression of Leukemic Cells Promotes Malignant Niche Formation and Bone Marrow Lodgment of Leukemic Cells in Chronic Myelogenous Leukemia2011
Author(s)
Kuroda J, Yamamoto M, Ashihara E, Nagoshi H, Kobayashi T, Matsumoto Y, Sasaki N, Shimura Y, Kiyota M, Nakayama R, Horiike S, Maekawa T, Taniwaki M
Organizer
The American Society of Hematology 53rd Annual Meeting and Exposition
Year and Date
2011-12-11
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[Presentation] Galectin-3 Is the Molecular Target for Overcoming Multidrug Resistance Due to the Cell Protection by Bone Marrow Leukemia Microenvironment in Chronic Myeloid Leukemia2011
Author(s)
Yamamoto M, Kuroda J, Kobayashi T, Sasaki N, Nagoshi H, Shimura Y, Kiyota M, Nakayama R, Horiike S, Ashihara E, Akaji K, Taniwaki M
Organizer
The American Society of Hematology 53rd Annual Meeting and Exposition
Year and Date
2011-12-11
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