CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma

Christopher Marlein, Rachel E. Piddock, Jayna J. Mistry, Lyubov Zaitseva, Charlotte Hellmich, Rebecca H. Horton, Zhigang Zhou, Martin J. Auger, Kristian M. Bowles, Stuart A. Rushworth

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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.

Original languageEnglish
Pages (from-to)2285-2297
Number of pages13
JournalCancer Research
Issue number9
Early online date8 Jan 2019
Publication statusPublished - May 2019

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