Lipidomic study of cell lines reveals differences between breast cancer subtypes

Abstract

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. Therefore, a novel noninvasive diagnostic tool for BC would give the opportunity of subtype-specific treatment and improved prospects for the patients. Heterogeneity of BC tumor subtypes is reflected in the expression levels of enzymes in lipid metabolism. The aim of the study was to investigate whether the subtype defined by the transcriptome is reflected in the lipidome of BC cell lines. A liquid chromatography mass spectrometry (LC-MS) platform was applied to analyze the lipidome of six cell lines derived from human BC cell lines representing different BC subtypes. We identified an increased abundance of triacylglycerols (TG) � C-48 with moderate or multiple unsaturation in fatty acyl chains and down-regulated ether-phosphatidylethanolamines (PE) (C-34 to C-38) in cell lines representing estrogen receptor and progesterone receptor positive tumor subtypes. In a cell line representing HER2-overexpressing tumor subtype an elevated expression of TG (� C-46), phosphatidylcholines (PC) and PE containing short-chained (� C-16) saturated or monounsaturated fatty acids were observed. Increased abundance of PC � C-40 was found in cell lines of triple negative BC subtype. In addition, differences were detected in lipidomes within these previously defined subtypes. 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 defined subtypes.

Analytical Platforms for the Determination of Phospholipid Turnover in Breast Cancer Tissue: Role of Phospholipase Activity in Breast Cancer Development

“…By applying UPLC-QTOF-MS, Eriksson et al revealed different lipidome profile between 7 BC cell lines, with the estrogen- and progesterone -receptor positive, showing a higher level of TGs and lower level of ether-PE [ 78 ]. Cell lines that are overexpressing the receptor for human endothelial factor, had a higher level of TGs, PCs, and PE with short chain fatty acids, but triple negative BC cell lines demonstrated an increased content of PCs.…”

“…This problem can be solved by introducing the isotopically labeled standards as the QC samples and it has been successfully applied for untargeted lipidomics of blood samples from patients suffering of Alzheimer’s disease [ 77 ], as well as for the lipidomics of breast cancer cell lines [ 78 ]. In the latter case, the differences in the lipid composition between various BC cell lines were discovered and quantified by LC-MS platform and statistical analysis.…”

Distinct photooxidation-induced cell death pathways lead to selective killing of human breast cancer cells

“…Non-tumorigenic human breast epithelial cells were more resistant to PDT than their malignant and more metastatic counterparts 13 . Up to date, there are no studies addressing a possible association of a defined lipid profile with aggressiveness and susceptibility to undergo different cell death subroutines upon massive oxidant species generation 22,23 . Therefore, the present study has focused on understanding the molecular pathways underlining these different cell behaviors upon photooxidative damage ( Figure 6 ).…”

Mass Spectrometry-Based Omics for the Characterization of Triple-Negative Breast Cancer Bio-Signature

“…regulation of the activity of nuclear transcription factors: peroxisome proliferator-activated receptors (PPARs), nuclear factor-κB (NF-κB) and sterol regulatory element-binding proteins (SREBPs) [ 40 ]. Glycerophospholipids (GPL) act as signaling molecules and have shown involvement in the regulation of migration, apoptosis and neurotransmission, while diacylglycerols (DG) are regarded as second messengers involved in apoptosis and mediation of signal transduction in cancer cells [ 41 ]. Nevertheless, altered expression of enzymes involved in lipid metabolism (synthesis, storage, activation and degradation) has been reported in breast tumors [ 42 ].…”

“…A comprehensive lipidomics study was performed by Eriksson et al [ 41 ] on several breast cancer cell lines including 2 representatives of TNBC (MDA-MB-231 and MDA-MB-436 with BRCA1 mutation) and MCF10A as control. The study concluded that there is an increased phosphatidylcholine synthesis correlated with TNBC cell lines: DG 32:0 and DG 34:0 were significantly more abundant in TNBC cell lines, while a decreased level of TG was also observed in these cell lines.…”