CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma

Marlein, Christopher, Piddock, Rachel E, Mistry, Jayna J, Zaitseva, Lyubov, Hellmich, Charlotte, Horton, Rebecca H, Zhou, Zhigang, Auger, Martin J, Bowles, Kristian M and Rushworth, Stuart A (2019) CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Cancer Research. ISSN 0008-5472

[img] PDF (Accepted_Manuscript) - Submitted Version
Restricted to Repository staff only until 08 January 2020.

Download (4054kB) | Request a copy

    Abstract

    Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move to cancer cells from their microenvironment, the metabolic consequences of this phenomenon have yet to be fully elucidated. Here we report that multiple myeloma (MM) cells use mitochondrial-based metabolism as well as glycolysis when located within the bone marrow microenvironment (BMM). The reliance of MM cells on oxidative phosphorylation was caused by intercellular mitochondrial transfer to MM cells from neighboring non-malignant bone marrow stromal cells (BMSC). This mitochondrial transfer occurred through tumor-derived tunneling nanotubes (TNT). Moreover, shRNA mediated knockdown of CD38 inhibits mitochondrial transfer and TNT formation in-vitro and blocks mitochondrial transfer and improves animal survival in vivo. This study describes a potential treatment strategy to inhibit mitochondrial transfer for clinical benefit and scientifically expands the understanding of the functional effects of mitochondrial transfer on tumor metabolism.

    Item Type: Article
    Additional Information: Copyright ©2019, American Association for Cancer Research.
    Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
    Faculty of Science > School of Pharmacy
    Depositing User: LivePure Connector
    Date Deposited: 11 Jan 2019 11:30
    Last Modified: 11 Jan 2019 11:30
    URI: https://ueaeprints.uea.ac.uk/id/eprint/69559
    DOI: 10.1158/0008-5472.CAN-18-0773

    Actions (login required)

    View Item