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

  1. Author:
    Khan, Imran
    Gril, Brunilde
    Hoshino, Ayuko
    Yang, Howard H
    Lee, Maxwell P
    Difilippantonio,Simone
    Lyden, David C
    Steeg, Patricia S

  2. Author Address

    Women 39;s Malignancies Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 37, Convent Drive, Room 1126, Bethesda, MD, 20892, USA. imran.khan@nih.gov., Children 39;s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA., Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA., School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan., Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, USA., Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA.,
    1. Year: 2022
    2. Date: Aug 08
    3. Epub Date: 2022 08 08
  2. Journal: Clinical & Experimental Metastasis
  4. Type of Article: Article
  1. 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. © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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External Sources

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  2. DOI: 10.1007/s10585-022-10182-7
  3. PMID: 35939247
  4. PII : 10.1007/s10585-022-10182-7

Library Notes

  1. Fiscal Year: FY2021-2022
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