Shangguan Lei, Li Xiaojie, Wang Zhe, Luo Zhuojing
Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Email:
Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
Zhonghua Zhong Liu Za Zhi. 2015 Nov;37(11):804-9.
OBJECTIVE: To investigate the effect of transforming growth factor-β1 (TGF-β1) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into cancer-associated fibroblasts(CAFs). METHODS: MSCs were cultured in α-MEM with recombinant human TGF-β1 or in tumor-conditioned medium.The expression of CAFs markers were detected by immunofluorescence and quantitative RT-PCR. RESULTS: The qRT-PCR assay showed that the expression of CAFs markers FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin were 9.92±2.16, 7.76±1.28, 3.04±0.95, 3.28±2.16, 2.13±0.71, 1.41±0.66, 2.25±0.86 and 1.38±0.56, respectively, significantly upregulated in the MSCs co-cultured with TGF-β1 or TCM. The relative levels of FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin mRNA in the TCM group were 7.52±1.76, 5.02±1.18, 1.98±1.19, 1.82±1.19, 2.95±0.86, 1.44±0.67, 2.08±0.74 and 1.47±0.55, respectively, indicating that MSCs can express CAFs phenotype.TGF beta signaling pathway inhibitor SB-431542 could inhibit the differentiation. Both immunofluorescence and Western blot confirmed the above results. CONCLUSIONS: TGF-β1 induces differentiation of local MSCs to CAFs by upregulating the expression of pSmad3, so as to further promote the growth of cancer cells.
目的：研究转化生长因子-β1（TGF-β1）对骨髓间充质干细胞（MSCs）向癌相关成纤维细胞（CAFs）分化的影响。 方法：将MSCs培养于含重组人TGF-β1的α-MEM培养基中或肿瘤条件培养基中。通过免疫荧光和定量RT-PCR检测CAFs标志物的表达。 结果：qRT-PCR检测显示，在与TGF-β1或肿瘤条件培养基共培养的MSCs中，CAFs标志物FAP、ACTA、CAV、CCL5、CXCR4、FSP1、SDF-1和波形蛋白的表达分别为9.92±2.16、7.76±1.28、3.04±0.95、3.28±2.16、2.13±0.71、1.41±0.66、2.25±0.86和1.38±0.56，显著上调。肿瘤条件培养基组中FAP、ACTA、CAV、CCL5、CXCR4、FSP1、SDF-1和波形蛋白mRNA的相对水平分别为7.52±1.76、5.02±1.18、1.98±1.19、1.82±1.19、2.95±0.86、1.44±0.67、2.08±0.74和1.47±0.55，表明MSCs可表达CAFs表型。TGF-β信号通路抑制剂SB-431542可抑制分化。免疫荧光和蛋白质印迹均证实了上述结果。 结论：TGF-β1通过上调pSmad3的表达诱导局部MSCs向CAFs分化，从而进一步促进癌细胞生长。
Zhonghua Zhong Liu Za Zhi. 2015-11
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