Bone Marrow Mesenchymal Stromal Cell-Derived Periostin Promotes B-ALL Progression by Modulating CCL2 in Leukemia Cells
Bone Marrow Mesenchymal Stromal Cell-Derived Periostin Promotes B-ALL Progression by Modulating CCL2 in Leukemia Cells
复制标题
骨髓间充质基质细胞来源的骨膜素通过调节白血病细胞中的 CCL2 促进 B-ALL 进展
DOI：
10.1016/j.celrep.2019.01.034
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发表时间：
2019-02-05
期刊：
影响因子：
8.8
通讯作者：
Ouyang, Gaoliang
中科院分区：
文献类型：
--
作者：
Ma, Zhenling;Zhao, Xueli;Ouyang, Gaoliang
骨膜蛋白（Periostin，POSTs）是一种多功能的细胞外组分，调节细胞-基质相互作用和细胞-细胞串扰。POR 4缺失显著降低小鼠的白血病负荷;然而，POR 4促进B细胞急性淋巴细胞白血病（B-ALL）进展的潜在机制在很大程度上仍然未知。在这里，我们证明了骨髓（BM）来源的间充质干细胞（BM-MSCs）表达更高水平的POR 4时，与B-ALL细胞在体外和体内共培养。骨髓间充质干细胞中的过氧化物酶缺乏显著降低体外和体内共培养的B-ALL细胞中CCL 2的表达。此外，泊洛沙姆治疗通过激活整联蛋白-ILK-NF-κ B途径增加B-ALL细胞中CCL 2的表达。相反，CCL 2处理通过STAT 3活化上调BM-MSC中的P019的表达。此外，在小鼠和B-ALL患者的BM中，POR 4表达与CCL 2水平之间存在正相关性。这些发现表明，B-ALL细胞衍生的CCL 2有助于BM-MSC衍生的POCL 2促进的白血病负荷增加。
Periostin (POSTN) is a multifunctional extracellular component that regulates cell-matrix interactions and cell-cell crosstalk. POSTN deletion significantly decreases leukemia burden in mice; however, the underlying mechanisms by which POSTN promotes B cell acute lymphoblastic leukemia (B-ALL) progression remain largely unknown. Here, we demonstrate that bone marrow (BM)-derived mesenchymal stromal cells (BM-MSCs) express higher levels of POSTN when co-cultured with B-ALL cells in vitro and in vivo. POSTN deficiency in BM-MSCs significantly decreases CCL2 expression in co-cultured B-ALL cells in vitro and in vivo. Moreover, POSTN treatment increases expression of CCL2 in B-ALL cells by activating the integrin-ILK-NF-kappa B pathway. Conversely, CCL2 treatment upregulates expression of POSTN in BM-MSCs via STAT3 activation. Furthermore, there is a positive correlation between POSTN expression and CCL2 level in the BM of mice and patients with B-ALL. These findings suggest that B-ALL cell-derived CCL2 contributes to the increased leukemia burden promoted by BM-MSC-derived POSTN.