Zhu Ni, Wang Huafang, Wei Jieping, Wang Binsheng, Shan Wei, Lai Xiaoyu, Zhao Yanmin, Yu Jian, Huang He
Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Mol Med Rep. 2016 Aug;14(2):1351-6. doi: 10.3892/mmr.2016.5389. Epub 2016 Jun 10.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are pivotal components of the leukemic microenvironment. BM-MSCs have been previously reported to promote the proliferation of leukemic cells. To further understand the molecular mechanisms of BM-MSC-induced proliferation of leukemic cells, the present study co-cultured acute lymphoblastic leukemia (ALL) Reh cells with BM-MSCs. The current study used methods including shRNA, flow cytometry, MTT, reverse transcription-quantitative polymerase chain reaction, ELISA and western blotting. The data of the present study demonstrated that BM‑MSCs promote the proliferation of Reh cells and the NR2F2 mRNA and protein levels were elevated in BM‑MSCs following co‑culture. Additionally, it was demonstrated that shRNA knockdown of NR2F2 inhibited BM‑MSC‑induced proliferation of Reh cells. Furthermore, following downregulation of NR2F2, vascular endothelial growth factor A (VEGFA) secretion by BM‑MSCs was reduced. The present study demonstrated that NR2F2 mediates BM‑MSC‑induced proliferation of Reh cells, partially via regulation of VEGFA. Disrupting microenvironmental support by targeting NR2F2 may be a potential therapeutic strategy for ALL.
骨髓间充质干细胞（BM-MSCs）是白血病微环境的关键组成部分。先前已有报道称BM-MSCs可促进白血病细胞的增殖。为了进一步了解BM-MSCs诱导白血病细胞增殖的分子机制，本研究将急性淋巴细胞白血病（ALL）Reh细胞与BM-MSCs进行共培养。本研究采用了包括短发夹RNA（shRNA）、流式细胞术、MTT法、逆转录-定量聚合酶链反应、酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法等方法。本研究的数据表明，BM-MSCs可促进Reh细胞的增殖，并且共培养后BM-MSCs中NR2F2的mRNA和蛋白质水平升高。此外，研究表明，通过shRNA敲低NR2F2可抑制BM-MSCs诱导的Reh细胞增殖。此外，在NR2F2下调后，BM-MSCs分泌的血管内皮生长因子A（VEGFA）减少。本研究表明，NR2F2介导BM-MSCs诱导的Reh细胞增殖，部分是通过调节VEGFA实现的。通过靶向NR2F2破坏微环境支持可能是ALL的一种潜在治疗策略。
