Leukemia cell to endothelial cell communication via exosomal miRNAs.

Recent findings indicate that specific microRNAs (miRNAs), such as those of the miR-17-92 cluster, may be responsible for regulating endothelial gene expression during tumor angiogenesis. Secreted miRNAs enclosed in exosomes also have an important role in cell-cell communication. To elucidate whether miRNAs secreted from neoplastic cells transfer into endothelial cells and are functionally active in the recipient cells, we investigated the effect of exosomal miRNAs derived from leukemia cells (K562) on human umbilical vein endothelial cells (HUVECs). As K562 cells released the miR-17-92 cluster, especially miR-92a, into the extracellular environment, K562 cells, transfected with Cy3-labeled pre-miR-92a, were co-cultured with HUVECs. Cy3-miR-92a derived from K562 cells was detected in the cytoplasm of HUVECs, and the Cy3-miR-92a co-localized with the signals of an exosomal marker, CD63. The expression of integrin α5, a target gene for miR-92a, was significantly reduced in HUVECs by exosomal miR-92a, indicating that exogenous miRNA via exosomal transport can function like endogenous miRNA in HUVECs. The most salient feature of this study is the exosome, derived from K562 cells with enforced miR-92a expression, did not affect the growth of HUVECs but did enhance endothelial cell migration and tube formation. Our results support the idea that exosomal miRNAs have an important role in neoplasia-to-endothelial cell communication.