Yi Xianlin, Li You, Hu XiaoGang, Wang FuBing, Liu Tiangang
Department of Urology, The Affiliated Cancer Hospital of Guangxi Medical University & Guangxi Cancer Research Institute, Nanning 530021,China.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, PR China.
J Cancer. 2021 Mar 15;12(10):2893-2902. doi: 10.7150/jca.48906. eCollection 2021.
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. Exosomes were extracted from LnCap, PC 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. 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 , 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. 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.
探索激素敏感性和激素抵抗性前列腺癌细胞外泌体中脂质的变化，并开发一种廉价且快速的技术来筛选前列腺癌基于脂质的生物标志物。从LnCap、PC和DU-145细胞中提取外泌体，并使用高通量质谱法定量分析其脂质组成。还使用基于聚乙二醇（PEG）沉淀的改良方法纯化LnCap前列腺癌细胞释放的外泌体。从LnCap细胞中提取的外泌体中磷脂酰胆碱、磷脂酰乙醇胺和磷脂酰肌醇脂质的比例高于整个LnCap细胞。溶血磷脂酰胆碱是磷脂酰胆碱代谢的有害中间产物，在LnCap细胞中未发现，但在外泌体中存在。LnCap、PC3和DU-145前列腺癌细胞的外泌体中的磷脂不同。这些细胞中涉及的主要脂质途径，即甘油磷脂代谢、自噬和铁死亡途径也不同。通过这种改良的PEG沉淀技术分离的外泌体在纯度上与使用商业试剂盒获得的外泌体相似。这项研究表明，磷脂酰胆碱及其有害产物溶血磷脂酰胆碱可能在激素敏感性前列腺癌中起重要作用。激素敏感性和激素抵抗性前列腺癌细胞中的磷脂外泌体代谢发生了变化。自噬和铁死亡的LPC脂质途径可能作为治疗靶点。使用改良的PEG沉淀法纯化前列腺癌细胞外泌体的可能性适用于癌症筛查。
