Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration
Mesenchymal stem cell-derived interleukin-6 and vascular endothelial growth factor promote breast cancer cell migration
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DOI：
10.1002/jcb.24212
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发表时间：
2012-11-01
影响因子：
4
通讯作者：
Normanno, Nicola
中科院分区：
文献类型：
--
作者：
De Luca, Antonella;Lamura, Luana;Normanno, Nicola
由间充质干细胞（MSCs）分泌的几种不同的细胞因子和生长因子被假设在乳腺癌的进展中发挥作用。通过使用一小组乳腺癌细胞系（MCF-7、T47D和SK-Br-3细胞），我们分析了白细胞介素-6 （IL-6）和血管内皮生长因子a （VEGF）在MSCs和乳腺癌细胞之间的串音中的作用。我们进行了迁移试验，在没有或存在抗vegf抗体贝伐单抗或抗il -6抗体的情况下，允许乳腺癌细胞在MSCs （msc - cm）的条件培养基中迁移，单独或联合使用。我们发现抗vegf和抗il -6抗体抑制乳腺癌细胞的迁移，并且联合使用具有更高的抑制作用。我们接下来评估了重组VEGF和IL-6蛋白对乳腺癌细胞生长和迁移的影响。IL-6和VEGF对乳腺癌细胞的增殖无显著影响。相比之下，VEGF和IL-6均能显著提高MCF-7、T47D和SK-Br-3细胞的迁移能力，且联合使用比单独使用更有效。VEGF和IL-6联合在乳腺癌细胞中产生了更显著、更持久的MAPK、AKT和p38MAPK细胞内信号通路的激活。这些结果表明msc分泌的IL-6和VEGF可能是维持乳腺癌细胞迁移的旁分泌因子。j .细胞。中国生物医学工程学报，2012,31(3):357 - 357。(C) 2012 Wiley期刊公司
Several different cytokines and growth factors secreted by mesenchymal stem cells (MSCs) have been hypothesized to play a role in breast cancer progression. By using a small panel of breast cancer cell lines (MCF-7, T47D, and SK-Br-3 cells), we analyzed the role of interleukin-6 (IL-6) and vascular endothelial growth factor A (VEGF) in the cross-talk between MSCs and breast cancer cells. We performed migration assays in which breast cancer cells were allowed to migrate in response to conditioned medium from MSCs (MSCs-CM), in absence or in presence of the anti-VEGF antibody bevacizumab or an anti-IL-6 antibody, alone or in combination. We found that anti-VEGF and anti-IL-6 antibodies inhibited the migration of breast cancer cells and that the combination had an higher inhibitory effect. We next evaluated the effects of recombinant VEGF and IL-6 proteins on breast cancer cell growth and migration. IL-6 and VEGF had not significant effects on the proliferation of breast carcinoma cells. In contrast, both VEGF and IL-6 significantly increased the ability to migrate of MCF-7, T47D and SK-Br-3 cells, with the combination showing a greater effect as compared with treatment with a single protein. The combination of VEGF and IL-6 produced in breast cancer cells a more significant and more persistent activation of MAPK, AKT, and p38MAPK intracellular signaling pathways. These results suggest that MSC-secreted IL-6 and VEGF may act as paracrine factors to sustain breast cancer cell migration. J. Cell. Biochem. 113: 33633370, 2012. (C) 2012 Wiley Periodicals, Inc.