Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX, USA.
J Hematol Oncol. 2013 Oct 8;6(1):72. doi: 10.1186/1756-8722-6-72.
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.
IGF 结合蛋白 2（IGFBP2）在癌症发展中的作用令人着迷。之前我们发现 IGFBP2 是支持造血干细胞（HSCs）活性的外在因素。
在这里，我们研究了 IGFBP2 在人白血病细胞中的作用以及逆转录病毒 AML1-ETO9a 移植急性髓系白血病（AML）小鼠模型中的作用。
IGFBP2 在某些人急性髓系白血病和急性淋巴细胞白血病（ALL）细胞中高度表达。抑制人白血病细胞内源性 IGFBP2 的表达导致细胞凋亡增加、迁移减少，AKT 和其他信号分子的活性降低。我们还研究了 IGFBP2 缺失对逆转录病毒 AML1-ETO9a 移植 AML 小鼠模型的影响。在供体 AML 细胞中缺失 IGFBP2 可显著降低移植小鼠中的白血病发生。IGFBP2 的缺失导致鼠 AML 细胞中 PTEN 表达上调和 AKT 激活下调。用 PTEN 抑制剂处理 IGFBP2 缺陷型 AML 细胞可恢复野生型集落形成能力。IGFBP2 的缺失还导致 AML 细胞向外周器官和组织浸润减少，表明 IGFBP2 是 AML 细胞从骨髓迁移所必需的。
IGFBP2 是促进急性白血病细胞存活和迁移的关键细胞自主因素。
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