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

J Nanobiotechnology. 2020 Nov 7;18(1):162. doi: 10.1186/s12951-020-00722-2.

Authors

Sara Busatto^{1

2

3}, Yubo Yang⁴, Sierra A Walker⁴, Irina Davidovich⁵, Wan-Hsin Lin⁶, Laura Lewis-Tuffin⁶, Panagiotis Z Anastasiadis⁶, Jann Sarkaria⁷, Yeshayahu Talmon⁵, Gregory Wurtz⁸, Joy Wolfram⁹

Affiliations

¹ Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL, 32224, USA. [email protected].
² Vascular Biology Program, Boston Children's Hospital, Boston, MA, USA. [email protected].
³ Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. [email protected].
⁴ Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL, 32224, USA.
⁵ Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute (RBNI), Technion-Israel Institute of Technology, 3200003, Haifa, Israel.
⁶ Department of Cancer Biology, Mayo Clinic Comprehensive Cancer, Center, Mayo Clinic, Jacksonville, FL, USA.
⁷ Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 55902, USA.
⁸ Department of Physics, University of North Florida, Jacksonville, FL, 32224, USA.
⁹ Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL, 32224, USA. [email protected].

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.

MeSH terms

Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Breast Neoplasms
Cell Line, Tumor
Endothelial Cells
Extracellular Vesicles / metabolism*
Humans
Lipoproteins, LDL / metabolism*
Macrophages
Monocytes
THP-1 Cells
Tumor Microenvironment

Substances

Lipoproteins, LDL

Grants and funding

R01 NS101721/NS/NINDS NIH HHS/United States