IL-6/STAT3 Plays a Regulatory Role in the Interaction Between Pancreatic Stellate Cells and Cancer Cells
IL-6/STAT3 Plays a Regulatory Role in the Interaction Between Pancreatic Stellate Cells and Cancer Cells
复制标题
DOI：
10.1007/s10620-015-4001-5
复制
发表时间：
2016-06-01
影响因子：
3.1
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
--
作者：
Hamada, Shin;Masamune, Atsushi;Shimosegawa, Tooru
胰腺星状细胞（PSC）在胰腺纤维化（胰腺癌的特征性特征）中发挥关键作用。尽管目前仍存在争议，但已有研究表明PSC通过调节癌细胞的细胞功能促进胰腺癌的进展。PSC产生大量IL-6，其通过信号转导和转录激活因子3（STAT 3）依赖性机制促进骨髓源性抑制细胞的积累。为了明确IL-6/STAT 3在PSCs与胰腺癌细胞相互作用中的作用，本研究采用永生化人PSCs条件培养液（PSC-CM）处理人胰腺癌细胞Panc-1和SUIT-2。使用Agilent的微阵列检查PSC-CM和IL-6中和对mRNA表达谱的影响。使用抗磷酸特异性抗体通过蛋白质印迹法评估STAT 3的活化。通过双室测定法检查细胞迁移。实时荧光定量逆转录PCR检测胰腺癌细胞EMT相关标志物的表达。IL-6的中和抑制了PSC-CM诱导的基因上调，包括补体因子B、脂质运载蛋白和趋化因子（C-C基序）配体20。IL-6抗体或STAT 3抑制剂（NSC 74859）抑制IL-6/STAT 3通路可抑制PSC-CM诱导的胰腺癌细胞迁移和EMT相关标志物（Snail和cadherin-2）的表达，IL-6/STAT 3通路调节PSC诱导的胰腺癌细胞EMT和基因表达的改变。
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis, a characteristic feature of pancreatic cancer. Although it is still controversial, previous studies have suggested that PSCs promote the progression of pancreatic cancer by regulating the cell functions of cancer cells. PSCs produce large amounts of IL-6, which promotes the accumulation of myeloid-derived suppressor cells via a signal transducers and activator of transcription 3 (STAT3)-dependent mechanism. But the role of IL-6/STAT3 pathway in the interaction between PSCs and pancreatic cancer cells remains largely unknown.To clarify the role of IL-6/STAT3 in the interaction between PSCs and cancer cells.Human pancreatic cancer cells (Panc-1 and SUIT-2 cells) were treated with conditioned medium of immortalized human PSCs (PSC-CM). The effects of PSC-CM and IL-6 neutralization on the mRNA expression profiles were examined using Agilent's microarray. Activation of STAT3 was assessed by Western blotting using an anti-phospho-specific antibody. Cellular migration was examined by a two-chamber assay. The expression of markers related to epithelial-mesenchymal transition (EMT) was assessed by real-time reverse transcription PCR.PSC-CM induced the activation of STAT3 in pancreatic cancer cells. Neutralization of IL-6 suppressed the PSC-CM-induced upregulation of genes including complement factor B, lipocalin, and chemokine (C-C motif) ligand 20. Inhibition of IL-6/STAT3 pathway by anti-IL-6 antibody or a STAT3 inhibitor (NSC74859) inhibited the PSC-CM-induced migration and the expression of EMT-related markers (Snail and cadherin-2) in pancreatic cancer cells.IL-6/STAT3 pathway regulates the PSC-induced EMT and alterations in gene expression in pancreatic cancer cells.