Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein
Background: Cancer cell-derived extracellular vesicles (EVs) have previously been shown to contribute to pre-metastatic niche formation. Specifically, aggressive tumors secrete pro-metastatic EVs that travel in the circulation to distant organs to modulate the microenvironment for future metastatic spread. Previous studies have focused on the interface between pro-metastatic EVs and epithelial/endothelial cells in the pre-metastatic niche. However, EV interactions with circulating components such as low-density lipoprotein (LDL) have been overlooked. Results: This study demonstrates that EVs derived from brain metastases cells (Br-EVs) and corresponding regular cancer cells (Reg-EVs) display different interactions with LDL. Specifically, Br-EVs trigger LDL aggregation, and the presence of LDL accelerates Br-EV uptake by monocytes, which are key components in the brain metastatic niche. Conclusions: Collectively, these data are the first to demonstrate that pro-metastatic EVs display distinct interactions with LDL, which impacts monocyte internalization of EVs. [Figure not available: see fulltext.]
Journal of Nanobiotechnology
Digital Object Identifier (DOI)
Busatto, S., Yang, Y., Walker, S.A., Davidovich, I., Lin, W.H., Lewis-Tuffin, L., Anastasiadis, P.Z., Sarkaria, J., Talmon, Y., Wurtz, G., Wolfram, J. (2020) Brain Metastases-Derived Extracellular Vesicles Induce Binding and Aggregation of Low-density Lipoprotein. Journal of Nanobiotechnology, 18(1), 162.