Mesenchymal Stromal Cells Protect Cancer Cells From ROS-induced Apoptosis and Enhance the Warburg Effect by Secreting STC1
Mesenchymal Stromal Cells Protect Cancer Cells From ROS-induced Apoptosis and Enhance the Warburg Effect by Secreting STC1
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DOI：
10.1038/mt.2011.259
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发表时间：
2012-02-01
影响因子：
12.4
通讯作者：
Prockop, Darwin J.
中科院分区：
文献类型：
--
作者：
Ohkouchi, Shinya;Block, Gregory J.;Prockop, Darwin J.
先前的研究表明，间充质基质细胞（MSC）通过上调和分泌斯钙素-1（STC 1）来增强细胞存活。这项研究表明，MSC衍生的STC 1通过解偶联氧化磷酸化，减少细胞内活性氧（ROS），并将代谢向糖酵解代谢模式转变来促进肺癌细胞的存活。MSC衍生的STC 1以STC 1依赖的方式上调损伤的A549细胞中的解偶联蛋白2（UCP 2）。UCP 2的敲低降低了MSC和重组STC 1（rSTC 1）减少A549群体中细胞死亡的能力。rSTC 1处理的A549细胞表现出ROS水平降低，线粒体膜电位（MMP），乳酸产生增加，所有这些都依赖于UCP 2的上调。我们的数据表明，MSC可以通过STC 1调节线粒体呼吸来促进细胞存活。
Previous studies have demonstrated that mesenchymal stromal cells (MSCs) enhance cell survival through upregulation and secretion of stanniocalcin-1 (STC1). This study shows that MSC-derived STC1 promotes survival of lung cancer cells by uncoupling oxidative phosphorylation, reducing intracellular reactive oxygen species (ROS), and shifting metabolism towards a more glycolytic metabolic profile. MSC-derived STC1 upregulated uncoupling protein 2 (UCP2) in injured A549 cells in an STC1-dependent manner. Knockdown of UCP2 reduced the ability of MSCs and recombinant STC1 (rSTC1) to reduce cell death in the A549 population. rSTC1-treated A549 cells displayed decreased levels of ROS, mitochondrial membrane potential (MMP), and increased lactate production, all of which were dependent on the upregulation of UCP2. Our data suggest that MSCs can promote cell survival by regulating mitochondrial respiration via STC1.