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CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma

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  • Accepted_Manuscript

    Accepted author manuscript, 3 MB, PDF-document

    Embargo ends: 8/01/20

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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.

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Original languageEnglish
JournalCancer Research
Early online date8 Jan 2019
DOIs
StateE-pub ahead of print - 8 Jan 2019
Peer-reviewedYes

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