Journal of Nanobiotechnology (Nov 2020)

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

  • 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

DOI
https://doi.org/10.1186/s12951-020-00722-2
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 15

Abstract

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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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