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

LR11对正常白细胞和白血病细胞的功能分析

• 批准号: 23591368
• 负责人: TAKEUCHI Masahiro
• 金额: $ 3.24万
• 依托单位: Chiba University
• 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-23591368/
• 关键词: 血液腫瘍学; 白血病; ニッチ; 低酸素; 細胞接着

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.

我们已经确定并表征了血管平滑肌细胞（SMC）中uPAR功能的调节因子LR 11（也称为SorLA或SORL 1）。LR 11 mRNA和细胞表面蛋白水平在未成熟白血病细胞中升高，进而导致急性白血病中sLR 11水平升高。结果：K562细胞表达低水平的LR 11蛋白，但在体外实验中，LR 11过表达（LR 11-ox）的K562细胞与假转染的K562细胞生长无明显差异。移植后4周移植LR 11-ox K562细胞的小鼠PB中白血病细胞的百分比显著高于移植mock细胞的小鼠。移植对照U937细胞的小鼠在移植后3周内全部死于白血病，而移植LR 11-KD U937细胞的小鼠存活时间明显延长。

项目成果

Serum soluble LR11 is a promising novel biomarker for B cell lymphoma

血清可溶性 LR11 是一种有前途的 B 细胞淋巴瘤新型生物标志物

• 发表时间: 2012
• 作者: 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
• 通讯作者: 中世古知昭

Serum soluble LR11 is a promising novel biomarker for malignant lymphoma

血清可溶性 LR11 是一种有前途的恶性淋巴瘤新型生物标志物

• 发表时间: 2011
• 作者: 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
• 通讯作者: 中世古知昭

The soluble form of LR11 is a regulator of hypoxia-induced, uPAR-mediated adhesion of immature hematological cells

LR11 的可溶形式是缺氧诱导、uPAR 介导的未成熟血液细胞粘附的调节剂

• 发表时间: 2013
• 期刊: J Biol Chem
• 影响因子: 4.8
• 作者: Keigo Nishii;Chiaki Nakaseko;Meizi Jiang;Naomi Shimizu;Masahiro Takeuchi;Wolfgang Johann Schneider;and Hideaki Bujo
• 通讯作者: and Hideaki Bujo

LR11 plays a critical role in leukemogenesis of AML by regulating cell adhes ion and homing ability

LR11通过调节细胞粘附和归巢能力在AML白血病发生中发挥关键作用

• 作者: 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
• 通讯作者: 武城英明

LR11 regulates the hypoxia-induced hematopoietic immature cell adhesion

LR11调节缺氧诱导的造血未成熟细胞粘附

• 发表时间: 2012
• 作者: 西居圭吾;武内正博;中世古知昭;武城英明ほか
• 通讯作者: 武城英明ほか