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. ORCID: https://orcid.org/0000-0003-1334-4526 and Rushworth, Stuart A. (2019) CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Cancer Research, 79 (9). pp. 2285-2297. ISSN 0008-5472

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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.

Item Type:	Article
Additional Information:	Copyright ©2019, American Association for Cancer Research.
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Pharmacy
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	11 Jan 2019 11:30
Last Modified:	24 Oct 2023 01:29
URI:	https://ueaeprints.uea.ac.uk/id/eprint/69559
DOI:	10.1158/0008-5472.CAN-18-0773

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