Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 37, Convent Drive, Room 1126, Bethesda, MD, 20892, USA.
Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
Clin Exp Metastasis. 2022 Oct;39(5):815-831. doi: 10.1007/s10585-022-10182-7. Epub 2022 Aug 8.
Tumor-derived exosomes have documented roles in accelerating the initiation and outgrowth of metastases, as well as in therapy resistance. Little information supports the converse, that exosomes or similar vesicles can suppress metastasis. We investigated the NME1 (Nm23-H1) metastasis suppressor as a candidate for metastasis suppression by extracellular vesicles. Exosomes derived from two cancer cell lines (MDA-MB-231T and MDA-MB-435), when transfected with the NME1 (Nm23-H1) metastasis suppressor, secreted exosomes with NME1 as the predominant constituent. These exosomes entered recipient tumor cells, altered their endocytic patterns in agreement with NME1 function, and suppressed in vitro tumor cell motility and migration compared to exosomes from control transfectants. Proteomic analysis of exosomes revealed multiple differentially expressed proteins that could exert biological functions. Therefore, we also prepared and investigated liposomes, empty or containing partially purified rNME1. rNME1 containing liposomes recapitulated the effects of exosomes from NME1 transfectants in vitro. In an experimental lung metastasis assay the median lung metastases per histologic section was 158 using control liposomes and 15 in the rNME1 liposome group, 90.5% lower than the control liposome group (P = 0.016). The data expand the exosome/liposome field to include metastasis suppressive functions and describe a new translational approach to prevent metastasis.
肿瘤来源的外泌体在加速转移的起始和生长以及治疗耐药性方面具有明确的作用。很少有信息支持相反的观点，即外泌体或类似的囊泡可以抑制转移。我们研究了 NME1（Nm23-H1）转移抑制因子作为细胞外囊泡抑制转移的候选物。从两种癌细胞系（MDA-MB-231T 和 MDA-MB-435）衍生的外泌体，当转染 NME1（Nm23-H1）转移抑制因子时，分泌的外泌体以 NME1 为主。这些外泌体进入受体肿瘤细胞，改变了它们的内吞模式，与 NME1 的功能一致，并与对照转染体的外泌体相比，抑制了体外肿瘤细胞的迁移和迁移。外泌体的蛋白质组分析揭示了多种可能发挥生物学功能的差异表达蛋白。因此，我们还制备并研究了脂质体，无论是空的还是含有部分纯化的 rNME1。含有 rNME1 的脂质体再现了 NME1 转染体来源的外泌体在体外的作用。在实验性肺转移测定中，每个组织切片的肺转移中位数分别为 158 个，使用对照脂质体和 15 个 rNME1 脂质体组，比对照脂质体组低 90.5%（P=0.016）。该数据将外泌体/脂质体领域扩展到包括抑制转移的功能，并描述了一种新的转化方法来预防转移。
