MSACL 2019 EU Abstract

Lipid Composition of Cancer-Derived Extracellular Vesicles and its Potential for the Identification of Body Fluid-Based Biomarkers for Breast Cancer diagnosis

Erika Dorado (1), M Luisa Doria (1), Anika Nagelkerke (2), Alvaro Perdones-Montero (1), Stefania Maneta-Stavrakaki (1), James S McKenzie (1), Ulrike Kauscher (2), R Charles Coombes (1), Jeremy Nicholson (1), Molly M Stevens (2), Zoltan Takats (1)
(1) Faculty of Medicine, Department of Surgery and Cancer, Imperial College London, London, United Kingdom (2) Faculty of Engineering, Department of Materials, Imperial College London, London, United Kingdom

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Erika Dorado (Presenter) Imperial College London >> POSTER (PDF)

Presenter Bio: Currently, I am a third year PhD student at Imperial College London and I am part of Professor Zoltan Takat’s group. My research is focused on the study of extracellular vesicles as body fluid-based biomarkers for cancer diagnosis. Specifically, I am interested in understanding the lipid composition of extracellular vesicles and their interactions during the cancer patient journey.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

Introduction:
Extracellular vesicles (EV) are secreted by cancer cells and are found in high concentrations in body fluids of cancer patients. These EV (including exosomes and microvesicles) play an important role in tumour development, progression and therapeutic response. EV are delimited by a lipid bilayer and contain proteins, nucleic acids and metabolites. Although EV have a great potential as liquid biopsies for early detection of breast cancer, the lipid composition of breast cancer-derived EV is unknown. The aim of this study is to characterise the lipid composition of EV released by breast cancer cells and its potential for the identification of body fluid-based biomarkers for breast cancer diagnosis.

Methods:
The lipid composition of EV and their parental cells were evaluated for nine breast cancer and two non-cancerous mammary cell lines. EV were isolated by size-exclusion chromatography. The shape of the EV was confirmed by cryo-electron microscopy and the number and size was defined by nanoparticle tracking analysis. Lipids extracted from EV and their parental cells were analysed by reverse-phase liquid chromatography mass-spectrometry. The data acquisition was performed in both positive and negative electrospray ionisation modes.

Results:
We found that breast cancer-derived EV were enriched in sphingomyelins, ceramides and lysophosphatidylethanolamines when compared to their parental cells. Furthermore, phospholipids such as phosphatidylcholine and phosphatidylethanolamine were found to be abundant in cancer-derived EV. Unsupervised and supervised analyses showed that EV released by breast cancer cells can be distinguished from those released by non-cancerous cells based on their lipid profile.

Conclusions:
This is the first global lipid profiling of EV released by breast cancer cell lines. Our findings demonstrate the potential of the lipid content of cancer-derived EV for the identification of biomarkers for breast cancer detection.