Phospholipid profiling enables to discriminate tumor- and non-tumor-derived human colon epithelial cells: Phospholipidome similarities and differences in colon cancer cell lines and in patient-derived cell samples

Hofmanová, Jiřina; Slavík, Josef; Ovesná, Petra; Tylichová, Zuzana; Dušek, Ladislav; Straková, Nicol; Vaculová, Alena Hyršlová; Cigánek, Miroslav; Kala, Zdeněk; Jira, M.; Penka, Igor; Kyclová, Jitka; Kolář, Zdeněk; Kozubı́k, Alois; Machala, Miroslav; Vondráček, Jan

doi:10.1371/journal.pone.0228010

Cited by 15 publications

(10 citation statements)

References 58 publications

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“…In the present study, we focused on two possible consequences of deregulated lipid metabolism in purified tumor epithelial cells: (i) deregulation of FA metabolism resulting in deregulated FA composition of tumor cells; (ii) altered lysoPL/PL ratios and increased levels of specific lysoPL species. This was based on our recent study, indicating that PL profiling can be successfully used to discriminate between normal and tumor cells isolated from CRC patients [37].…”

Section: Discussionmentioning

confidence: 99%

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Hofmanová

Slavík

Cigánek

et al. 2021

IJMS

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The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM+ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

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Section: Discussionmentioning

confidence: 99%

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Hofmanová

Slavík

Cigánek

et al. 2021

IJMS

Self Cite

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“…Alterations in the composition and distribution of PLs in cells, tissues and biofluids are associated with cancer [22] and have been explored as potential diagnostic or prognostic biomarkers in a variety of cancers, such as breast cancer [23], prostate cancer [24], lung cancer [25] and ovarian cancer [26]. PL analysis has also been applied in CRC to investigate the suitability of model colon cell lines [27] and threedimensional culture systems [13] for lipidomic analysis in CRC studies. Accumulation of PL species reflects the increased amounts of polyunsaturated fatty acids (PUFAs), a phenomenon that has previously been observed in CRC tissues [28].…”

Section: Introductionmentioning

confidence: 99%

Alterations in complex lipids in tumor tissue of patients with colorectal cancer

et al. 2021

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Background Accumulating evidence indicates alterations in lipid metabolism and lipid composition in neoplastic tissue. Earlier nuclear magnetic resonance studies showed that the contents of major lipid groups, such as triacylglycerols, phospholipids and cholesterol, are changed in colon cancer tissue. Methods In this study, a more detailed analysis of lipids in cancer and tumor adjacent tissues from colorectal cancer patients, using liquid chromatography–mass spectrometry, allowed for comparison of 199 different lipids between cancer tissue and tumor adjacent tissue using principal component analysis. Results Significant differences were found in 67 lipid compounds between the two types of tissue; many of these lipid compounds are bioactive lipids such as ceramides, lysophospholipids or sterols and can influence the development of cancer. Additionally, increased levels of phospholipids and sphingolipids were present, which are major components of the cell membrane, and increases in these lipids can lead to changes in cell membrane properties. Conclusions This study showed that many complex lipids are significantly increased or decreased in colon cancer tissue, reflecting significant alterations in lipid metabolism. This knowledge can be used for the selection of potential molecular targets of novel anticancer strategies based on the modulation of lipid metabolism and the composition of the cell membrane in colorectal cancer cells.

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“…Since primary cells are better at simulating in vivo gene expression conditions as compared to immortalized cell lines [ 39 , 40 ], mouse primary fibroblast cells were utilized to assess pZGFP and pRGFP expression profiles. Due to technical challenges and early cell senescence, GFP expression was only assessed at Day 1, 2, 3, and 5 post-transfection using Lipid GTA.…”

Section: Resultsmentioning

confidence: 99%

Limited expression of non-integrating CpG-free plasmid is associated with increased nucleosome enrichment

et al. 2020

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CpG-free pDNA was reported to facilitate sustained transgene expression with minimal inflammation in vivo as compared to CpG-containing pDNA. However, the expression potential and impact of CpG-free pDNA in in vitro model have never been described. Hence, in this study, we analyzed the transgene expression profiles of CpG-free pDNA in vitro to determine the influence of CpG depletion from the transgene. We found that in contrast to the published in vivo studies, CpG-free pDNA expressed a significantly lower level of luciferase than CpG-rich pDNA in several human cell lines. By comparing novel CpG-free pDNA carrying CpG-free GFP (pZGFP: 0 CpG) to CpG-rich GFP (pRGFP: 60 CpGs), we further showed that the discrepancy was not influenced by external factors such as gene transfer agent, cell species, cell type, and cytotoxicity. Moreover, pZGFP exhibited reduced expression despite having equal gene dosage as pRGFP. Analysis of mRNA distribution revealed that the mRNA export of pZGFP and pRGFP was similar; however, the steady state mRNA level of pZGFP was significantly lower. Upon further investigation, we found that the CpG-free transgene in non-integrating CpG-free pDNA backbone acquired increased nucleosome enrichment as compared with CpG-rich transgene, which may explain the observed reduced level of steady state mRNA. Our findings suggest that nucleosome enrichment could regulate non-integrating CpG-free pDNA expression and has implications on pDNA design.

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Phospholipid profiling enables to discriminate tumor- and non-tumor-derived human colon epithelial cells: Phospholipidome similarities and differences in colon cancer cell lines and in patient-derived cell samples

Cited by 15 publications

References 58 publications

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Alterations in complex lipids in tumor tissue of patients with colorectal cancer

Limited expression of non-integrating CpG-free plasmid is associated with increased nucleosome enrichment

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