TY - JOUR
T1 - IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells
AU - Chen, Xiaoli
AU - Zheng, Junke
AU - Zou, Yizhou
AU - Song, Chun
AU - Hu, Xuemei
AU - Zhang, Chengcheng
N1 - Funding Information:
Support to C. C. Z. is from NIH grant 1R01CA172268, the Leukemia and Lymphoma Society Scholar Award 260071, DOD PR093256, and CPRIT RP100402.
PY - 2013
Y1 - 2013
N2 - Background: 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). Methods and results. 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. Results: 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. Conclusion: IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells.
AB - Background: 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). Methods and results. 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. Results: 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. Conclusion: IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells.
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U2 - 10.1186/1756-8722-6-72
DO - 10.1186/1756-8722-6-72
M3 - Article
C2 - 24191913
AN - SCOPUS:84884999455
SN - 1756-8722
VL - 6
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 72
ER -