Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis‐mediated vascular remodeling

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. AML cells secrete angiogenic factors to remodel vasculature and acquire chemoresistance; however, antiangiogenic drugs are often ineffective in AML treatment. Cancer cell‐derived exosomes can induce angiogenesis, but their r...

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Bibliographic Details
Published in:Journal of cellular physiology 2019-07, Vol.234 (7), p.10602-10614
Main Authors: Wang, Bin, Wang, Xiaoting, Hou, Diyu, Huang, Qian, Zhan, Weiwu, Chen, Canwei, Liu, Jingru, You, Ruolan, Xie, Jieqiong, Chen, Ping, Huang, Huifang
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Adults
Angiogenesis
Antiangiogenics
Apoptosis
Apoptosis - genetics
Cancer
Cell migration
Cell proliferation
Chemoresistance
Drug Resistance, Neoplasm - genetics
Endothelial cells
Exosomes
Exosomes - genetics
Gene expression
Glycolysis
Glycolysis - genetics
Growth factors
Human Umbilical Vein Endothelial Cells
Humans
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - pathology
Myeloid leukemia
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Ribonucleic acid
RNA
Signal Transduction - genetics
Umbilical vein
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor Receptor-1 - genetics
Vascular endothelial growth factor receptors
vascular remodeling
Vascular Remodeling - genetics
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Summary:Acute myeloid leukemia (AML) is the most common type of leukemia in adults. AML cells secrete angiogenic factors to remodel vasculature and acquire chemoresistance; however, antiangiogenic drugs are often ineffective in AML treatment. Cancer cell‐derived exosomes can induce angiogenesis, but their role in vascular remodeling during AML is unclear. Here, we found that exosomes secreted by AML cells promoted proliferation and migration and tube‐forming activity of human umbilical vein endothelial cells (HUVECs), whereas HUVECs conferred chemoresistance to AML cells. AML cell‐derived exosomes contained vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) messenger RNA and induced VEGFR expression in HUVECs. Furthermore, they enhanced glycolysis, which correlated with HUVEC proliferation, tube formation, and resistance to apoptosis. Thus, AML cells secrete VEGF/VEGFR‐containing exosomes that induce glycolysis in HUVECs leading to vascular remodeling and acquisition of chemoresistance. These findings may contribute to the development of novel therapeutic strategies targeting exosomes in AML.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.27735