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

AbstractAcute 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 c hemoresistance 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 resistanc e 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.

Source: Journal of Cellular Physiology - November 11, 2018 Category: Cytology Authors: Bin Wang, Xiaoting Wang, Diyu Hou, Qian Huang, Weiwu Zhan, Canwei Chen, Jingru Liu, Ruolan You, Jieqiong Xie, Ping Chen, Huifang Huang Tags: ORIGINAL RESEARCH ARTICLE Source Type: research