间质基质细胞通过分泌 STC1 来保护癌细胞免受 ROS 诱导的细胞凋亡，并增强瓦博格效应。
Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and enhance the Warburg effect by secreting STC1.
机构信息
Department of Respiratory Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan.
出版信息
Mol Ther. 2012 Feb;20(2):417-23. doi: 10.1038/mt.2011.259. Epub 2011 Dec 6.
Abstract
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.
摘要
先前的研究表明间充质基质细胞 (MSCs) 通过上调和分泌 STC1 来增强细胞存活。本研究表明，MSC 衍生的 STC1 通过解偶联氧化磷酸化、减少细胞内活性氧 (ROS) 和将代谢转向更糖酵解代谢特征来促进肺癌细胞的存活。MSC 衍生的 STC1 以 STC1 依赖的方式在上皮 A549 细胞损伤中上调解偶联蛋白 2 (UCP2)。敲低 UCP2 降低了 MSC 和重组 STC1 (rSTC1) 减少 A549 细胞群体中细胞死亡的能力。rSTC1 处理的 A549 细胞显示出降低的 ROS 水平、线粒体膜电位 (MMP) 和增加的乳酸产生，所有这些都依赖于 UCP2 的上调。我们的数据表明，MSCs 可以通过 STC1 调节线粒体呼吸来促进细胞存活。
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