Effective internalization of U251-MG-secreted exosomes into cancer cells and characterization of their lipid components

Exosomes, the natural vehicles of various biological molecules, have been examined in several research fields including drug delivery. Although understanding of the biological functions of exosomes has increased, how exosomes are transported between cells remains unclear. We hypothesized that cell tropism is important for effective exosomal intercellular communication and that parental cells regulate exosome movement by modulating constituent exosomal molecules. Herein, we demonstrated the strong translocation of glioblastoma-derived exosomes (U251(exo)) into their parental (U251) cells, breast cancer (MDA-MB-231) cells, and fibrosarcoma (HT-1080). Furthermore, disruption of proteins of U251(exo) by enzymatic treatment did not affect their uptake. Therefore, we focused on lipid molecules of U251(exo) with the expectation that they are crucial for effective incorporation of U251(exo) by cancer cells. Phosphatidylethanolamine was identified as a unique lipid component of U251-MG cell-derived extracellular vesicles. From these results, valuable insight is provided into the targeting of U251(exo) to cancer cells, which will help to develop a cancer-targeted drug delivery system. (C) 2014 Elsevier Inc. All rights reserved.