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

Research output: Contribution to journalArticle

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. [Figure not available: see fulltext.]

Original languageEnglish (US)
Article number162
JournalJournal of Nanobiotechnology
Volume18
Issue number1
DOIs
StatePublished - Dec 1 2020

Keywords

  • Brain metastasis
  • Extracellular vesicles
  • Lipoproteins
  • Macrophages
  • Pre-metastatic niche

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science

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