MSACL 2019 EU Abstract

Lipidomic Study of Cell Lines Reveals Differences between Breast Cancer Subtypes

Finnur Freyr Eiriksson (1,3,4), Martha Kampp Nøhra (1,2), Sigridur Klara Bödvarsdottir (2,3), Helga Margret Ögmundsdottir (2,3) Margret Thorsteinsdottir (1,2,4)
(1) Faculty of Pharmaceutical Sciences, University of Iceland, (2) Biomedical Center University of Iceland, (3) Faculty of Medicine, University of Iceland, (4) ArcticMass, Reykjavík, Iceland

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Finnur Freyr Eiriksson (Presenter) University of Iceland

Presenter Bio: I have a M.Sc. Degree in pharmaceutical sciences from the University of Iceland since 2010 and in 2019 I received my Ph.D. in Biomedical Sciences from the University of Iceland, with a focus on method development of lipidomics in cancer. I have co-supervised eight M.Sc. students from the faculty of Pharmaceutical Sciences, University of Iceland in the field of analytical chemistry with a focus on lipid analysis with mass spectrometry and the use of chemometrics for method development and for multivariate data analysis.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

INTRODUCTION: Breast cancer (BC) is the most prevalent type of cancer in women in western countries. BC mortality has not declined despite early detection by screening, indicating the need for better informed treatment decisions. It is acknowledged that lipid metabolism is altered in tumours and cancer cells and that the heterogeneity of BC tumour subtypes is reflected in the expression levels of enzymes in lipid metabolism. Therefore, a novel non-invasive diagnostic tool for BC based on lipidomic analysis of plasma samples would allow for subtype-specific treatment and improved prospects for the patients.

OBJECTIVES: The aim of the study was to investigate whether the subtypes defined by the transcriptome are reflected in the lipidome of BC cell lines.
METHODS: BC cell lines representing, tumours positive for estrogen (ER) and progesterone receptor (PgR), CAMA-1, MCF-7, T-47D; HER2 overexpressing tumours, SK-BR-3; and ER, PgR and HER2 negative (triple negative), MDA-MB-231 and MDA-MB-436; were selected as tumour cell lines. MCF10A, a human immortalized mammary epithelial non-cancerous cell line, was used as a reference. The lipidome of human BC cell lines representing different BC subtypes was analysed with an ultra-performance liquid chromatography coupled to a quadruple time-of flight mass spectrometry (UPLC-QTOF-MS) platform. Multivariate data analysis was conducted utilizing principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA).

RESULTS: We identified an increased abundance of triacylglycerols (TG) ≥ C-48 with moderate or multiple unsaturation in fatty acyl chains and down-regulation of ether-phosphatidylethanolamines (PE) (C-34 to C-38) in BC cell lines representing ER- and PgR-positive tumour subtypes. In a BC cell line representing the HER2-overexpressing tumour subtype an elevated expression of TG (≤ C-46), phosphatidylcholines (PC) and PE containing short-chained (≤ C-16) saturated or monounsaturated fatty acids was observed. Increased abundance of PC ≥ C-40 was found in cell lines of the triple-negative BC subtype. In addition, differences were detected in lipidomes within the previously defined subtypes.

CONCLUSION: We conclude that subtypes defined by the transcriptome are indeed reflected in differences in the lipidome and, furthermore, potentially biologically relevant differences may exist within these previously defined subtypes.