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.

Department of Clinical and Molecular Pathology Institute of Molecular and Translational Medicine Faculty of Medicine Palacký University and University Hospital 779 00 Olomouc Czech Republic

Department of Cytokinetics Institute of Biophysics of the Czech Academy of Sciences 612 65 Brno Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University 625 00 Brno Czech Republic

Department of Pharmacology and Toxicology Veterinary Research Institute 621 00 Brno Czech Republic

Department of Surgery University Hospital 779 00 Olomouc Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University 602 00 Brno Czech Republic

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