网络首发:2014-05-20,
纸质出版:2014
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肾癌分泌IL-8激活ERK促进间充质干细胞迁移的机制[J]. 中山大学学报(医学科学版), 2014,35(2).
Secretion of IL-8 from Renal Cell Carcinoma Promotes Mesenchymal Stem Cells Migration via Activation of ERK signaling[J]. Journal of Sun Yat-sen University (Medical Sciences), 2014, 35(2).
【目的】 拟探讨肾癌内IL-8的分泌水平及其对骨髓间充质干细胞(MSC)的调节机制
探讨其在归巢中的作用机制?【方法】 ELISA法检测肾癌患者血清以及肾癌细胞分泌的IL-8;免疫组织化学和RT-PCR检测MSC表面IL-8受体表达;迁移实验观察IL-8对MSC的迁移作用;Western blotting 法检测IL-8对MSC内ERK的激活作用?【结果】研究发现正常人群的血液中IL-8为210.4 pg/mL
而肾癌患者血液中IL-8升高至526.7 pg/mL
肾癌细胞株786-O和ACHN均可以分泌IL-8;在MSC细胞中表达IL-8的受体基因CXCR2
肾癌细胞分泌IL-8可以通过CXCR2受体促进MSC迁移?进一步研究发现
IL-8刺激后可以明显提高MSC内ERK的磷酸化水平?【结论】肾癌可以分泌IL-8 能够通过CXCR2受体激活MSC内ERK信号通路
进而促进MSC迁移归巢
这可能是肾癌促进MSC归巢的重要机制之一?
【Objective】 Mesenchymal stem cells (MSC) are multifunctional adult stem cells
which can be homing to tumors
play an important role in the tumor development and metastasis. However
how MSC home to renal cell carcinoma (RCC) remains unclear. 【Methods】 The secretion of IL-8 from renal cancer patient and renal cancer cells was examined by ELISA method. The expression of IL-8 receptor was tested by RT-PCR and immunohistochemistry staining. The migration of MSC stimulated by IL-8 was detected by Migration assay. The phosphorylation of ERK by IL-8 in MSC was detected by Western blotting. 【Results】 It was found that IL-8 was significantly increased in RCC patients. RCC cell lines 786-O and ACHN cells could secrete high levels of IL-8 respectively. IL-8 CXCR2 receptor was highly expressed in MSC cells
the secretion of IL-8 by RCC cells could promote MSC migration through CXCR2. Further study demonstrated that IL-8 stimulation could significantly up regulated the phosphorylation of ERK via CXCR2. 【Conclusion】 RCC cells could secrete IL-8
which could promote MSC migration through CXCR2 by the activation of ERK signaling pathway. This may be one of the important mechanisms of the MSC homing to RCC tissues.
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