The n-10 Fatty Acids Family in the Lipidome of Human Prostatic Adenocarcinoma Cell Membranes and Extracellular Vesicles

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.

Uncovering the Exosomes Diversity: A Window of Opportunity for Tumor Progression Monitoring

“…In the beginning, it was thought that exosomes were a fairly homogeneous class of extracellular vesicles, but more recent experimental pieces of evidence have highlighted the enormous diversity in the exosome category so as to define distinct subtypes released for example from the apical or basolateral surface of tumor cells [90]. The various subtypes of exosomes differ according to biogenesis [91], lipid composition [92], surface markers [93], and obviously for the cargo [94].…”

Fatty Acids and Membrane Lipidomics in Oncology: A Cross-Road of Nutritional, Signaling and Metabolic Pathways

“…The analytical approach for the unambiguous characterization and discrimination of positional and geometrical fatty acid isomers having the 16:1 structure is crucial for the determination of the sapienic acid presence. We described in detail the protocol of fatty acid analysis, which includes a crucial derivatization step to localize the double bond position, using the well-known dimethyl disulfide (DMDS) adducts and its diagnostic fragmentation in mass spectrometry [ 6 , 10 , 63 , 79 ]. It must be added that such derivatization procedure and mass spectra can be performed by regular equipment in chemical labs, and do not require specialized and expensive instrumentation.…”

“…In the same study, the biophysical properties of the cell membranes were monitored by two-photon fluorescent microscopy, using Laurdan as a dye, showing that the supplementation of sapienic acid, with respect to its positional isomer palmitoleic acid, increased fluidity in several regions, evidently correlated with the formation and distribution of n-10 MUFA and PUFA in lipid domains. Following the interest in extracellular vesicles EVs (exosomes) as relevant sites for cancer metabolism and diagnostics [ 84 ], we investigated the presence of the n-10 fatty acid family, comparing membrane phospholipids and EVs of prostate cancer cell lines with different degrees of aggressiveness: PC3 (prostate cancer) and LNCaP (prostate derived from metastatic site: left supraclavicular lymph node), the former being more aggressive [ 10 ]. We found that 12–13% of the membrane fatty acids of these cell lines were composed of n-10 fatty acids, with the sapienic acid content >7%.…”

“…We gathered the literature on how fatty acids are implicated in tumor onset and progression and how the cancer lipidome reflects the activation of the de novo synthetic pathways. In this overview, we wish also to highlight our own work on the discovery of a family of MUFA positional isomers, the n-10 family, as new biomarkers of the metabolic shift that allows human cells to build up the first endogenous PUFA component, sebaleic acid [ 10 ]. The review also covers the link between obesity and cancer in order to understand why and when lipid supply causes health complications, highlighting specific fatty acids for their biological effects, signaling and contribution to the membrane properties that influence cell growth and death.…”

The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

“…Indeed, it has been shown that EVs released by tumor cells during malignant progression contain proteins [24], nucleic acids [25,26], and lipids [27] that can be used as markers of the neoplastic and metastatic phenotype. An example is the identification of caveolin-1, a protein associated with the metastatic behavior of tumors, in plasma EVs.…”