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Open AccessArticle

Lipidomic Analysis of Cells and Extracellular Vesicles from High- and Low-Metastatic Triple-Negative Breast Cancer

1
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan
2
Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan
3
Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan
*
Authors to whom correspondence should be addressed.
Present address: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
Present address: Laboratory for Neural Cell Dynamics, RIKEN Center for Brain Science 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Metabolites 2020, 10(2), 67; https://doi.org/10.3390/metabo10020067 (registering DOI)
Received: 13 December 2019 / Revised: 2 February 2020 / Accepted: 7 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Intercellular Metabolome)
Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted from almost all cells including cancer. Cancer-derived EVs contribute to cancer progression and malignancy via educating the surrounding normal cells. In breast cancer, epidemiological and experimental observations indicated that lipids are associated with cancer malignancy. However, lipid compositions of breast cancer EVs and their contributions to cancer progression are unexplored. In this study, we performed a widely targeted quantitative lipidomic analysis in cells and EVs derived from high- and low-metastatic triple-negative breast cancer cell lines, using supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry. We demonstrated the differential lipid compositions between EVs and cells of their origin, and between high- and low-metastatic cell lines. Further, we demonstrated EVs from highly metastatic breast cancer accumulated unsaturated diacylglycerols (DGs) compared with EVs from lower-metastatic cells, without increasing the amount in cells. The EVs enriched with DGs could activate the protein kinase D signaling pathway in endothelial cells, which can lead to stimulated angiogenesis. Our results indicate that lipids are selectively loaded into breast cancer EVs to support tumor progression.
Keywords: angiogenesis; diacylglycerol; endothelial cells; extracellular vesicles; exosomes; lipidomics; protein kinase D angiogenesis; diacylglycerol; endothelial cells; extracellular vesicles; exosomes; lipidomics; protein kinase D
MDPI and ACS Style

Nishida-Aoki, N.; Izumi, Y.; Takeda, H.; Takahashi, M.; Ochiya, T.; Bamba, T. Lipidomic Analysis of Cells and Extracellular Vesicles from High- and Low-Metastatic Triple-Negative Breast Cancer. Metabolites 2020, 10, 67.

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