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:10.1186/s12951-020-00722-2

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

Houston Methodist

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English (US)
Article number	162
Pages (from-to)	162
Journal	Journal of Nanobiotechnology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12951-020-00722-2
State	Published - Nov 7 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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10.1186/s12951-020-00722-2

Cite this

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title = "Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein",

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.",

keywords = "Brain metastasis, Extracellular vesicles, Lipoproteins, Macrophages, Pre-metastatic niche",

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

note = "Funding Information: This research was funded by Arizona State University-Mayo Clinic Collaborative Fund (JW), Mayo Clinic Eagles Cancer Telethon (JW), and the Mayo Clinic Cancer Center Neuro-Oncology Program. Acknowledgements Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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doi = "10.1186/s12951-020-00722-2",

language = "English (US)",

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T1 - Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein

AU - Busatto, Sara

AU - Yang, Yubo

AU - Walker, Sierra A.

AU - Davidovich, Irina

AU - Lin, Wan Hsin

AU - Lewis-Tuffin, Laura

AU - Anastasiadis, Panagiotis Z.

AU - Sarkaria, Jann

AU - Talmon, Yeshayahu

AU - Wurtz, Gregory

AU - Wolfram, Joy

N1 - Funding Information: This research was funded by Arizona State University-Mayo Clinic Collaborative Fund (JW), Mayo Clinic Eagles Cancer Telethon (JW), and the Mayo Clinic Cancer Center Neuro-Oncology Program. Acknowledgements Publisher Copyright: © 2020, The Author(s).

PY - 2020/11/7

Y1 - 2020/11/7

N2 - 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.

AB - 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.

KW - Brain metastasis

KW - Extracellular vesicles

KW - Lipoproteins

KW - Macrophages

KW - Pre-metastatic niche

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

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