The molecular mechanism by which saturated lysophosphatidylcholine attenuates the metastatic capacity of melanoma cells

Abstract

Lysophophatidylcholine (Lyso PC ) is an abundant constituent in human plasma. Patients with malignant cancer diseases have attenuated Lyso PC plasma levels, and thus Lyso PC has been examined as a metabolic biomarker for cancer prediction. Preclinical studies have shown that solid tumor cells drastically degrade Lyso PC s by incorporating their free fatty acids into cell membrane phospholipids. In this way, Lyso PC C18:0 reduced the metastatic spread of murine melanoma B16.F10 cells in mice. Although membrane rigidification may have a key role in the attenuation of metastasis, evidence for this has yet to be shown. Therefore, the present study aimed to determine how Lyso PC reduces the metastatic capacity of B16.F10 cells. Following cellular preincubation with Lyso PC C18:0 at increasing concentrations and lengths of time, cell migration was most significantly attenuated with 450 μ m Lyso PC C18:0 at 72 h. Biosensor measurements suggest that, despite their abundance in B16.F10 cells, Lyso PC ‐sensitive G protein‐coupled receptors do not appear to contribute to this effect. Instead, the attenuated migration appears to result from changes in cell membrane properties and their effect on underlying signaling pathways, most likely the formation of focal adhesion complexes. Treatment with 450 μ m Lyso PC C18:0 activates protein kinase C ( PKC )δ to phosphorylate syndecan‐4, accompanied by deactivation of PKC α. Subsequently, focal adhesion complex formation was attenuated, as confirmed by the reduced activity of focal adhesion kinase ( FAK ). Interestingly, 450 μ m Lyso PC C18:1 did not affect FAK activity, explaining its lower propensity to affect migration and metastasis. Therefore, membrane rigidification by Lyso PC C18:0 appears to prevent the formation of focal adhesion complexes, thus affecting integrin activity as a key for metastatic melanoma spread.

Chiroptical spectroscopy and metabolomics for blood‐based sensing of pancreatic cancer

“…As lysophosphatidylcholine(20:5) is known for its anticancer abilities, the enormous m / z signal decrease thereof in the PC patients indicated uncontrolled cell proliferation, and tumor growth . Furthermore, this decrease may also reflect a major disruption of lipid metabolism affecting primarily the lecithin‐cholesterol acyltransferase enzyme system in the liver.…”

Integrin Activation Contributes to Lower Cisplatin Sensitivity in MV3 Melanoma Cells by Inducing the Wnt Signalling Pathway

“…Cells were then centrifuged and supernatant was collected and submitted to protein quantification by Pierce™ BCA Protein Assay Kit (Thermo Fisher Scientific Inc, Waltham, MA USA). SDS-Page and Western Blot were performed, as described in [ 54 ]. Membranes were incubated with rabbit anti- E-cadherin (Santa Cruz Biotechnology, Dallas, TX, USA), mouse anti-GAPDH (GeneTex, Irvine, CA, USA), and goat anti-rabbit and donkey anti-mouse IgG HRP-conjugated (Santa Cruz Biotechnology, Dallas, TX, USA) diluted in 1% BSA solution.…”

Metabolism of sleep and aging: Bridging the gap using metabolomics

“…Three metabolites were found to be replicated in at least two studies -lysoPC 18:0, lysoPC 18:2 and dihydrosphingosine (Supplementary information S1). Plasma lysoPC 18:0 was found to decrease in two studies [106,123] which has been recently shown to increase cellular membrane rigidity in vivo [125] suggesting alteration in membrane integrity by means of changes in membrane lipid composition plays a critical role in development of AD. The role of membrane lipids in AD is also manifested by upregulation of sphingomyelin in a study based in the United States using MS based shotgun lipidomics [126].…”