Zhang Yue-Mei, Zhang Zhi-Ming, Guan Quan-Lin, Liu Yong-Qi, Wu Zhi-Wei, Li Jin-Tian, Su Yun, Yan Chun-Lu, Luo Ya-Li, Qin Jie, Wang Qian, Xie Xiao-Dong
Department of Ophthalmology, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities, Lanzhou, Gansu 730000, P.R. China.
Exp Ther Med. 2017 Oct;14(4):2983-2991. doi: 10.3892/etm.2017.4909. Epub 2017 Aug 8.
The initiation and progression of various types of tumors, such as lung neoplasms, are driven by a population of cells with stem cell properties and their microenvironment. Bone marrow mesenchymal stem cells (BM-MSCs) in long-term culture may exhibit spontaneous changes in stem cell biological properties, including malignant transformations; however, the molecular mechanisms of this have not been fully elucidated. In the present study, a BM-MSC and lung cancer A549 cell co-culture system was utilized to investigate how the tumor microenvironment may spontaneously change the proliferation, migration and differentiation of BM-MSCs. It was demonstrated that the lung cancer A549 microenvironment is able to induce changes in the cell morphology, proliferation, karyotype, cytoskeleton and migration ability of BM-MSCs . Compared with the control group BM-MSCs, the expression of Ras, phosphorylated-extracellular regulated protein kinases, nuclear factor-κB, P62 and B-cell lymphoma 2 (Bcl-2) proteins in groups of co-cultured BM-MSCs increased significantly (P<0.05) and the expression of P53, Bcl-2 associated X protein and caspase-3 protein decreased significantly (P<0.05). The mechanisms responsible for the changes observed in BM-MSCs may be related to abnormal expression of related genes in the ERK signaling pathway.
包括肺肿瘤在内的各类肿瘤的发生和进展是由具有干细胞特性的细胞群体及其微环境驱动的。长期培养的骨髓间充质干细胞(BM-MSCs)可能会出现干细胞生物学特性的自发变化,包括恶性转化;然而,其分子机制尚未完全阐明。在本研究中,利用BM-MSC与肺癌A549细胞共培养系统,研究肿瘤微环境如何自发改变BM-MSCs的增殖、迁移和分化。结果表明,肺癌A549微环境能够诱导BM-MSCs的细胞形态、增殖、核型、细胞骨架和迁移能力发生变化。与对照组BM-MSCs相比,共培养的BM-MSCs组中Ras、磷酸化细胞外调节蛋白激酶、核因子-κB、P62和B细胞淋巴瘤2(Bcl-2)蛋白的表达显著增加(P<0.05),而P53、Bcl-2相关X蛋白和半胱天冬酶-3蛋白的表达显著降低(P<0.05)。BM-MSCs中观察到的变化的机制可能与ERK信号通路中相关基因的异常表达有关。