乳腺癌转移中的磷脂酰胆碱和溶血磷脂酰胆碱分析（英文）

Analysis of Phosphatidylcholines(PCs) and Lysophosphatidylcholines(Lyso PCs) in Metastasis of Breast Cancer Cells

我们以前曾报道花生四烯酸(arachidonic acid,AA)代谢产物可以促进乳腺癌细胞增殖和迁移.为了进一步寻找维持高转移乳腺癌细胞中AA高水平代谢的内源机制,深入探求AA代谢促进乳腺癌细胞转移的分子机理,我们应用HPLC/ESI/MSn技术检测和分析了乳腺癌MCF-7和高转移乳腺癌LM-MCF-7细胞中溶血磷脂酰胆碱(lysophosphatidylcholines,Lyso PCs)和磷脂酰胆碱(phosphatidylcholines,PCs)的成分和含量.发现了10种Lyso PC的含量在LM-MCF-7细胞中显著高于MCF-7细胞,有6种PC可水解产生AA,它们在LM-MCF-7细胞中的含量显著低于MCF-7细胞,提示这些溶血磷脂含量的升高和磷脂含量的降低可能与乳腺癌转移相关.在LM-MCF-7细胞中,COX-2抑制剂吲哚美辛(indomethacin,Indo)和LOX抑制剂(nordihydroguaiaretic acid,NDGA)共同作用可明显下调c PLA2的活性,应用HPLC-ESI-MSn技术比较c PLA2活性下调前后LM-MCF-7细胞中Lyso PC和PC含量的变化,发现其中4种PC可被c PLA2水解产生AA.还发现,细胞内Lyso PC与PC的比值可以反映c PLA2的活性.通过以上研究进一步证实了由c PLA2活性调节的AA释放及代谢对乳腺癌转移具有重要作用.

The important role of phospholipids in many processes including cell cycle regulation, inflammation and tumorigenesis is increasingly becoming the focus of research. Previously we found that cytosolic phospholipase A2 （cPLA2） is over-expressed in breast cancer cells. Here, we assessed the profiles of phosphatidylcholines （PCs） and lysophosphatidylcholines （LysoPCs） that were mediated by cPLA2 in breast cancer cells. MCF-7 and LM-MCF-7 （with high metastatic potential） cell lines were used as models and the profiles of phospholipids were analyzed by HPLC/ESI/MSn. Our results showed that the levels of 10 species of LysoPCs were higher in LM-MCF-7 cells than that in MCF-7 cells. Meanwhile, six species of PCs that may produce arachidonic acid （AA） and associated LysoPCs were lower in LM-MCF-7 cells than that in MCF-7 cells. Furthermore, we identified that 4 out of 6 species of PCs were responsible for the generation of AA mediated by cPLA2 in LM-MCF-7 cells. The increased ratio of LysoPCs to PCs corresponds to the activation level of cPLA2. Thus, we conclude that 4 identified species of PCs and 4 corresponding species of LysoPCs mediated by cPLA2, as well as the up-regulation and activation of cPLA2, may involve in the metastasis of breast cancer cells.