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半乳糖凝集素-1 驱动的胰腺星状细胞中 SDF-1 的上调促进胰腺癌转移。

Galectin-1-driven upregulation of SDF-1 in pancreatic stellate cells promotes pancreatic cancer metastasis.

机构信息

Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China; Department of General Surgery, Affiliated Hospital of Nanjing University of TCM, Jiangsu Province Hospital of TCM, Nanjing 210029, China.

Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Pancreas Institute, Nanjing Medical University, Nanjing 210029, China.

出版信息

Cancer Lett. 2017 Jul 1;397:43-51. doi: 10.1016/j.canlet.2017.03.024. Epub 2017 Mar 21.

Abstract

Galectin-1, mainly expressed in activated pancreatic stellate cells (PSCs), is involved in many important cancer-related processes. However, very little is known how Galectin-1 modulates PSCs and subsequently impacts pancreatic cancer cells (PCCs). Our chemokine antibody array and in vitro studies demonstrates that Galectin-1 induces secretion of stromal cell-derived factor-1(SDF-1) in PSCs by activating NF-κB signaling. The secreted SDF-1 increases migration and invasion of PCCs. Knockdown of Galectin-1 and inhibitor-mediated blockade of SDF-1 as well as its ligand CXCR4 and NF-κB verifies the findings. In vivo experiment by knockdown of Galectin-1 in PSCs further demonstrates the conclusion. Collectively, the present studies demonstrate that Galectin-1-driven production of SDF-1 in PSCs through activation of NF-κB promotes metastasis in PDAC, offering a potential target in the treatment of pancreatic cancer.

摘要

半乳糖凝集素-1(Galectin-1)主要在活化的胰腺星状细胞(PSCs)中表达,参与许多重要的癌症相关过程。然而,关于 Galectin-1 如何调节 PSCs 以及随后如何影响胰腺癌细胞(PCCs)的信息知之甚少。我们的趋化因子抗体阵列和体外研究表明,Galectin-1 通过激活 NF-κB 信号通路诱导 PSCs 分泌基质细胞衍生因子-1(SDF-1)。分泌的 SDF-1 增加了 PCCs 的迁移和侵袭。Galectin-1 的敲低以及 SDF-1 及其配体 CXCR4 和 NF-κB 的抑制剂阻断实验验证了这一发现。通过在 PSCs 中敲低 Galectin-1 的体内实验进一步证实了这一结论。综上所述,本研究表明,Galectin-1 通过激活 NF-κB 驱动 PSCs 中 SDF-1 的产生促进了 PDAC 的转移,为胰腺癌的治疗提供了一个潜在的靶点。

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