Molecular and cellular effects of tumor microenvironment-specific Galectin-3 in leukemia

肿瘤微环境特异性 Galectin-3 在白血病中的分子和细胞作用

• 批准号: 23591403
• 负责人: KURODA Junya
• 金额: $ 3.24万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591403/
• 关键词: ガレクチン-3; 慢性骨髄性白血病; 骨髄腫瘍環境; 分子標的; FTY720; アポトーシス; BIM; BID; MCL-1; ガレクチンー3; 腫瘍環境; 治療抵抗性

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,

本文研究了肿瘤微环境特异性诱导半乳糖凝集素-3 （Gal-3）在慢性髓性白血病（CML）白血病细胞中的分子生物学作用。Gal-3通过激活ERK和AKT以及抑制细胞外serpina1 -白蛋白复合物促进白血病细胞的增殖。Gal-3还诱导抗凋亡MCL-1的表达，引起CML细胞对分子靶向药物和基因毒性药物的耐药。有趣的是，体内Gal-3的表达促进了白血病细胞在骨髓中的沉积。最后，我们的研究表明，除了目前使用的分子靶向药物，如伊马替尼或达沙替尼，联合使用蛋白磷酸酶-2激活剂可以有效地克服Gal-3的一系列促白血病作用。

项目成果

Fingolimod (FTY720) Overcomes the Resistance to Tyrosine Kinase Inhibitors Via Dual Activation of BIM and BID in Chronic Myelogenous Leukemia

芬戈莫德 (FTY720) 通过 BIM 和 BID 的双重激活克服慢性粒细胞白血病对酪氨酸激酶抑制剂的耐药性

• 发表时间: 2012
• 作者: 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.
• 通讯作者: Taniwaki M.

Galectin-3 protects CML leukemic cells by antagonizing SERPINA1-albumin complex

Galectin-3 通过拮抗 SERPINA1-白蛋白复合物保护 CML 白血病细胞

• 发表时间: 2012
• 作者: 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
• 通讯作者: Taniwaki M

Leukemia microenvironment-specific galectin-3 expression promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia

白血病微环境特异性半乳糖凝集素3表达促进慢性粒细胞白血病的耐药性和骨髓沉积

• 发表时间: 2012
• 作者: 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
• 通讯作者: Taniwaki M

Galectin-3 Is the Molecular Target for Overcoming Multidrug Resistance Due to the Cell Protection by Bone Marrow Leukemia Microenvironment in Chronic Myeloid Leukemia

Galectin-3是慢性粒细胞白血病中骨髓白血病微环境的细胞保护作用，克服多药耐药性的分子靶点

• 发表时间: 2011
• 作者: Yamamoto M;Kuroda J;Kobayashi T;Sasaki N;Nagoshi H;Shimura Y;Kiyota M;Nakayama R;Horiike S;Ashihara E;Akaji K;Taniwaki M
• 通讯作者: Taniwaki M

慢性骨髄性白血病に対するチロシンキナーゼ阻害剤治療

酪氨酸激酶抑制剂治疗慢性粒细胞白血病

• 发表时间: 2012
• 作者: Tokunaga K;Yamaguchi S;Shimomura T;Suzushima H;Mitsuya H;Asou N.;黒田純也
• 通讯作者: 黒田純也