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Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein

Posted on 2020-11-08 - 08:18
Abstract 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.

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AUTHORS (11)

Sara Busatto
Yubo Yang
Sierra A. Walker
Irina Davidovich
Wan-Hsin Lin
Laura Lewis-Tuffin
Panagiotis Z. Anastasiadis
Jann Sarkaria
Yeshayahu Talmon
Gregory Wurtz
Joy Wolfram
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