Abstract
A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid, a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid has attracted attention as a novel marker of cancer cell plasticity. Here, we analyzed fatty acids, including the n-10 fatty acid contents, and for the first time, compared cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9–13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 versus delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.
Highlights
Lipid biosynthesis and cancer cell growth are strongly connected to each other in multiple aspects of replication, signaling and energy metabolism
The percentages of each fatty acid in the total fatty acid content of PC3 and LNCaP cell membrane phospholipids and their extracellular vesicles (EV) were obtained (% relative quantities, % rel. quant.) and the values are shown in Table 1, and in Table 2 as mean ± standard error of the mean (S.E.M) of n = 8 replicates
We consider the fatty acid composition of cell membrane phospholipids shown in Table 1 with a particular interest for n-10 fatty acids, following sapienic acid to sebaleic acid transformation, in order to envisage differences of fatty acid composition between the two cell types
Summary
Lipid biosynthesis and cancer cell growth are strongly connected to each other in multiple aspects of replication, signaling and energy metabolism. After biosynthesis of two saturated fatty acids (SFA), palmitic (C16:0) and stearic acids (C18:0), monounsaturated fatty acids (MUFA) must be formed by delta-9 desaturase with the formation of palmitoleic (9cis-C16:1) and oleic (9cis-C18:1) acids, to gain cell membrane fluidity [3,4]. Such membrane status triggers a cascade of proliferation signals maintaining stemness, tumor formation and metastasis in breast, colon and prostate cancers [5,6].
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