Metastasis suppressor NME1 in exosomes or liposomes conveys motility and migration inhibition in breast cancer model systems

Clin Exp Metastasis. 2022 Oct;39(5):815-831. doi: 10.1007/s10585-022-10182-7. Epub 2022 Aug 8.

Abstract

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.

Keywords: Breast cancer metastasis; Exosomes; Liposomes; Metastasis suppressor; NME.

MeSH terms

  • Breast Neoplasms*
  • Cell Line, Tumor
  • Exosomes*
  • Female
  • Humans
  • Liposomes
  • Lung Neoplasms* / secondary
  • NM23 Nucleoside Diphosphate Kinases* / genetics
  • NM23 Nucleoside Diphosphate Kinases* / metabolism
  • Neoplasm Metastasis
  • Proteomics

Substances

  • Liposomes
  • NM23 Nucleoside Diphosphate Kinases
  • NME1 protein, human