Abstract
Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three approaches identified significant difference in the lipid profiles of the three prostate cancer cell lines (DU145, LNCaP and 22RV1) and one non-malignant cell line (PNT1a). Specific lipid classes and species, such as phospholipids (e.g., phosphatidylethanolamine 18:1/16:0 and 18:1/18:1) and cholesteryl esters, detected by LC-ESI-MS/MS, allowed statistical separation of all four prostate cell lines. Lipid mapping by FTIR revealed that variations in these lipid classes could also be detected at a single cell level, however further investigation into this approach would be needed to generate large enough data sets for quantitation. Visualisation by fluorescence microscopy showed striking variations that could be observed in lipid staining patterns between cell lines allowing visual separation of cell lines. In particular, polar lipid staining by a fluorescent marker was observed to increase significantly in prostate cancer lines cells, when compared to PNT1a cells, which was consistent with lipid quantitation by LC-ESI-MS/MS and FTIR spectroscopy. Thus, multiple technologies can be employed to either quantify or visualise changes in lipid composition, and moreover specific lipid profiles could be used to detect and phenotype prostate cancer cells.
Highlights
A hallmark of cancer cells is their metabolic reprogramming, which enables them to rapidly proliferate, migrate and alter their microenvironment to facilitate metastasis
Lipid profiles varied between prostate cancer cell lines, an observation which reflects the heterogeneous nature of this disease, but which may provide a useful tool for the phenotyping of prostate cancer
Differences observed in lipid profiles of prostate cells lines by LC-ESI-mass spectrometry (MS)/MS, were able to be detected at an individual cell level by Fourier transform infrared spectroscopy (FTIR) spectroscopy and by fluorescent markers
Summary
A hallmark of cancer cells is their metabolic reprogramming, which enables them to rapidly proliferate, migrate and alter their microenvironment to facilitate metastasis. Characteristics of metabolic alterations in cancer cells include significant increases in glucose and glutamine consumption [1], and alterations in lipid transport and utilisation [2]. Overexpression of www.oncotarget.com fatty acid synthase (FAS) is associated with an increased risk of mortality from prostate cancer, which rises further when combined with a loss of the phosphatase and tensin homolog (PTEN) tumour suppressor gene [4]. The loss or inactivation of PTEN induces an upregulation of FAS that is mediated via the activation of phosphoinositide 3-kinase (PI3K)/AKT pathway [5]. Concomitant activation of PI3K/AKT and MAPK pathways increases sterol regulatory element-binding protein (SREBP)dependent lipogenesis [6]; compounding the downstream effects of androgen-regulated (AR) metabolism [7], lipid composition and architecture of cellular membranes. The altered synthesis and metabolism of lipids in prostate cancer cells and changes to lipid profiles is being recognised as a key feature of the pathogenesis [8, 9]
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