State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China; College of Life Sciences, Henan Agricultural University, Zhengzhou, Henan 450002, China.
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China.
Cell Rep. 2019 Feb 5;26(6):1533-1543.e4. doi: 10.1016/j.celrep.2019.01.034.
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-κB 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.
骨膜蛋白 (POSTN) 是一种多功能细胞外成分，可调节细胞-基质相互作用和细胞间通讯。POSTN 缺失可显著降低小鼠白血病负担；然而，POSTN 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不清楚。在这里，我们证明骨髓 (BM) 来源的间充质基质细胞 (BM-MSCs) 在体外和体内与 B-ALL 细胞共培养时表达更高水平的 POSTN。BM-MSCs 中 POSTN 的缺失可显著降低体外和体内共培养的 B-ALL 细胞中 CCL2 的表达。此外，POSTN 通过激活整合素-ILK-NF-κB 通路增加 B-ALL 细胞中 CCL2 的表达。相反，CCL2 通过激活 STAT3 上调 BM-MSCs 中 POSTN 的表达。此外，B-ALL 小鼠和患者 BM 中 POSTN 表达与 CCL2 水平之间存在正相关。这些发现表明，B-ALL 细胞衍生的 CCL2 有助于由 BM-MSC 衍生的 POSTN 促进的白血病负担增加。
