PDF(Pubmed)
Abstract：
The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.
摘要：
神经元细胞粘附分子（NCAM）上的聚唾液酸（polySia）的表达称为NCAM-聚唾液酸化，这与肿瘤细胞的迁移和侵袭以及侵袭性临床状态密切相关。因此，在临床治疗中，选择合适的药物来阻断肿瘤细胞的迁移是非常重要的。在这项研究中,我们提出，与CMP和低分子量肝素（LMWH）相比，乳铁蛋白（LFcinB11）可能是抑制NCAM聚唾液酸化的更好候选物，这是根据我们的核磁共振研究确定的。此外，中性粒细胞胞外陷阱（NETs）代表了细胞死亡过程中最戏剧性的阶段，NETs的释放与自身免疫性疾病和炎症性疾病的发病机制有关，被提议参与肾小球肾炎，慢性肺病,脓毒症,和血管疾病。在这项研究中,还确定了使用LFcinB11作为抑制剂抑制NET释放的分子机制。基于这些结果,LFcinB11被认为是抑制NCAM聚唾液酸化和NETs释放的双功能抑制剂。
