Changes in phospholipid metabolism in exosomes of hormone-sensitive and hormone-resistant prostate cancer cells

Abstract

Background: To explore the changes in lipids in exosomes of hormone-sensitive and hormone-resistant prostate cancer cells and develop an inexpensive and rapid technique for screening lipid-based biomarkers of prostate cancer. Methods: Exosomes were extracted from LnCap, PC 3 and DU-145 cells, and their lipid composition was analyzed quantitatively using high-throughput mass spectrometry. Exosomes released by LnCap prostate cancer cells were also purified using a modified procedure based on polyethylene glycol (PEG) precipitation. Results: Exosomes extracted from LnCap cells contained higher proportions of phosphatidyl choline, phosphatidyl ethanolamine and phosphatidyl inositol lipids than whole LnCap cells. Lysophosphatidylcholine, a harmful intermediate product of phosphatidylcholine metabolism in vivo , was not found in LnCap cells but in exosomes. Phospholipids were different in exosomes from LnCap, PC3 and DU-145 prostate cancer cells. The main lipid pathways involved, i.e., glycerophospholipid metabolism, autophagy, and ferroptosis pathways, were also different in these cells. Exosomes isolated by this modified PEG precipitation technique were similar in purity to those obtained using a commercial kit. Conclusions: This study demonstrates that phosphatidylcholine and its harmful product lysophosphatidylcholine may play important roles in hormone-sensitive prostate cancer. Phospholipid exosome metabolism was changed in hormone-sensitive and hormone-resistant prostate cancer cells. The LPC, lipid pathway of autophagy and ferroptosis may act as therapeutic targets. The possibility of purifying prostate cancer cell exosomes using modified PEG precipitation is suitable for cancer screening.

Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules

“…Metabolomics (Figure S11, Supporting Information) and proteomics (Figure S12, Supporting Information) on exosomes isolated from serum‐containing and serum‐deprived media of old MEFs (passage 8) revealed that the metabolomic profile of exosomes from starvation group was significantly different from that of the control group, and differential proteins were mainly enriched in nucleic acid metabolic process. Lysophosphatidylcholine (LPC) is a harmful metabolite of lipids and is associated with inflammation [ 38 ] and oxidative stress. [ 39 ] This is a representative obsolete molecule highly accumulated in the exosomes expelled by the starvation old cells.…”

Determination of Glycerophospholipids in Biological Material Using High-Performance Liquid Chromatography with Charged Aerosol Detector HPLC-CAD—A New Approach for Isolation and Quantification

“…Most authors provide their data as a percentage of the total phospholipids, and absolute values are usually expressed as the amount of phospholipid per 10 6 cells or otherwise the tissue mass are not available. In the case of prostate cells, the comparison of the percentage content of individual GPLs with the results of some authors [ 45 , 46 ] showed a large convergence, but there were considerable differences with the results of other authors [ 47 ]. It was presumed that, apart from the various methods of determination of GPL, the underlying cause was the various lipid isolation procedures applied, which was also demonstrated in this study.…”

Ferroptosis and the ubiquitin-proteasome system: exploring treatment targets in cancer

“…An overabundance of PUFAs can cause the Fenton reaction to convert them into hydroxyl radicals, which in turn can cause an overabundance of lipid peroxide and, in turn, cause cells to enter ferroptosis ( Dierge et al, 2021 ; Mishima and Conrad, 2022 ). Phosphatidyl ethanolamine (PE) makes up roughly 15%–25% of the phospholipids in the membranes of other organelles compared to about 40%–45% of the total phospholipids in the inner membrane of mitochondria ( Feng and Stockwell, 2018 ; Yi et al, 2021 ). Data indicates that PE contributes to the ferroptosis triggered by arachidonic acid (AA) and its analogues.…”