IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells.
IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells.
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DOI：
10.1186/1756-8722-6-72
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发表时间：
2013-10-08
影响因子：
28.5
通讯作者：
Zhang CC
中科院分区：
文献类型：
--
作者：
Chen X;Zheng J;Zou Y;Song C;Hu X;Zhang CC
IGF结合蛋白2（IGFBP 2）在癌症发展中的作用是有趣的。先前我们鉴定IGFBP 2为支持造血干细胞（HSC）活性的外在因子。在此，我们研究了IGFBP 2在人白血病细胞和逆转录病毒AML 1-ETO 9a移植急性髓性白血病（AML）小鼠模型中的作用。IGFBP 2在某些人AML和急性淋巴细胞白血病（ALL）细胞中高度表达。在人白血病细胞中抑制内源性IGFBP 2的表达导致凋亡增加和迁移减少，并且一致地导致AKT和其他信号分子的活化减少。我们还研究了IGFBP 2基因敲除在逆转录病毒AML 1-ETO 9a移植AML小鼠模型中的作用。供体AML细胞中IGFBP 2的缺失显著降低了移植小鼠的白血病发展。在小鼠AML细胞中，IGFBP 2的缺乏导致PTEN表达上调和AKT活化下调。用PTEN抑制剂处理IGFBP 2缺陷型AML细胞恢复了野生型集落形成能力。IGFBP 2的缺失也导致AML向外周器官和组织的浸润减少，表明IGFBP 2是AML细胞从骨髓中迁移出来所必需的。IGFBP 2是促进急性白血病细胞存活和迁移的关键细胞自主因子。
The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs). Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model. IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibition of expression of endogenous IGFBP2 in human leukemia cells led to elevated apoptosis and decreased migration and, consistently, to decreased activation of AKT and other signaling molecules. We also studied the effects of IGFBP2 knockout in the retroviral AML1-ETO9a transplantation AML mouse model. The deletion of IGFBP2 in donor AML cells significantly decreased leukemia development in transplanted mice. Lack of IGFBP2 resulted in upregulation of PTEN expression and downregulation of AKT activation, in the mouse AML cells. The treatment of IGFBP2 deficient AML cells with a PTEN inhibitor restored the wild-type colony forming ability. The deletion of IGFBP2 also led to decreased AML infiltration into peripheral organs and tissues, suggesting that IGFBP2 is required for the migration of AML cells out of bone marrow. IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells.
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影响因子：
4.8
作者：
Foulstone, Emily J.;Zeng, Li;Holly, Jeff M. P.
通讯作者：
Holly, Jeff M. P.
影响因子：
8
作者：
Ben-Shmuel, A.;Shvab, A.;Ben-Ze'ev, A.
通讯作者：
Ben-Ze'ev, A.
影响因子：
--
作者：
Ranke, MB;Elmlinger, M
通讯作者：
Elmlinger, M
DOI：
10.1016/s0167-4889(00)00136-1
发表时间：
2001-02-05
影响因子：
5.1
作者：
Besnard, V;Corroyer, S;Clement, A
通讯作者：
Clement, A
DOI：
10.1073/pnas.1120375109
发表时间：
2012-02-28
影响因子：
11.1
作者：
Holmes, Kristen M.;Annala, Matti;Zhang, Wei
通讯作者：
Zhang, Wei