CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma
CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma
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DOI：
10.1158/0008-5472.can-18-0773
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发表时间：
2019-05-01
期刊：
影响因子：
11.2
通讯作者：
Rushworth, Stuart A.
中科院分区：
文献类型：
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作者：
Marlein, Christopher R.;Piddock, Rachel E.;Rushworth, Stuart A.
代谢调节对于癌细胞的起始、增殖和扩散是必要的。虽然线粒体已被证明可以从微环境中转移到癌细胞中，但这种现象的代谢后果尚未完全阐明。在这里，我们报告了多发性骨髓瘤细胞在骨髓微环境中使用基于骨髓的代谢以及糖酵解。多发性骨髓瘤细胞对氧化磷酸化的依赖是由相邻的非恶性骨髓基质细胞向多发性骨髓瘤细胞的线粒体转移引起的。这种线粒体转移通过肿瘤衍生的隧道纳米管（TNT）发生。此外，shRNA介导的CD38敲低在体外抑制线粒体转移和TNT形成，并在体内阻断线粒体转移和改善动物存活。本研究描述了一种潜在的治疗策略，以抑制线粒体转移的临床效益和科学扩展的线粒体转移对肿瘤metabolisation.Significance的功能影响的理解：多发性骨髓瘤依赖于氧化磷酸化和糖酵解后收购的线粒体从骨髓微环境。
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 cells use mitochondrial-based metabolismas well as glycolysis when located within the bone marrow microenvironment. The reliance of multiple myeloma cells on oxidative phosphorylation was caused by intercellular mitochondrial transfer to multiple myeloma cells from neighboring nonmalignant bone marrow stromal cells. 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.Significance: Multiple myeloma relies on both oxidative phosphorylation and glycolysis following acquisition of mitochondria from its bone marrow microenvironment.