来自胰腺星状细胞的NGF通过PI3K/AKT/GSK信号通路诱导胰腺癌增殖和侵袭。

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Journal of Cellular and Molecular Medicine Pub Date : 2020-05-01 Epub Date: 2020-04-15 DOI:10.1111/jcmm.15265
Jie Jiang, Jun Bai, Tao Qin, Zheng Wang, Liang Han
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引用次数: 32

摘要

胰腺癌是一种持续的高致死率疾病,肿瘤微环境在胰腺癌的发展过程中起着关键作用。本研究主要研究了胰腺星状细胞-胰腺癌细胞(PSCs-PC细胞)共培养体系中神经生长因子(NGF)/原肌球蛋白相关激酶A (TrkA)对胰腺癌增殖和侵袭的影响。使用Transwell作为共培养系统,将PC细胞与psc模型直接无接触共培养。采用实时荧光定量PCR、免疫荧光、Western blotting或ELISA检测培养体系中NGF和TrkA的表达。用小干扰RNA转染调节PC细胞中TrkA的表达。采用Matrigel Transwell实验研究其对肿瘤侵袭的促进作用。在我们的研究中,NGF/TrkA在PSCs-PC细胞共培养系统中过表达,促进PC细胞的侵袭和增殖。si-TrkA影响上皮-间质转化相关基因。此外,NGF/TrkA通过激活PI3K/AKT/GSK信号通路调控PC细胞的增殖和侵袭。本研究证实NGF/TrkA在共培养系统中通过激活PI3K/AKT/GSK信号级联促进PC细胞的增殖和侵袭,为PC患者提供了潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway.

NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway.

NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway.

NGF from pancreatic stellate cells induces pancreatic cancer proliferation and invasion by PI3K/AKT/GSK signal pathway.

Pancreatic cancer (PC) is a continuously high lethal disease, and the tumour microenvironment plays a pivotal role during PC progression. Herein, we focus on that the Nerve growth factor (NGF)/Tropomyosin-related kinase A (TrkA), in pancreatic stellate cells-pancreatic cancer cells (PSCs-PC cells) co-culture system, influences PC proliferation and invasion. The model of PC cells and PSCs was directly co-cultured in a no-touch manner, using the Transwell as the co-culture system. NGF and TrkA expression was measured in cultured system by real-time PCR, immunofluorescence, Western blotting analysis or ELISA. Small interfering RNA transfection was used to regulate the expression of TrkA in PC cells. The promotion of cancer invasion was investigated using Matrigel Transwell assay. In our study, NGF/TrkA is overexpressed in PSCs-PC cells co-culture system and promotes the invasion and proliferation of PC cells. And the epithelial-mesenchymal transition-related genes are influenced by si-TrkA. What's more, NGF/TrkA regulates the PC cell proliferation and invasion via activation of PI3K/AKT/GSK signalling. The present study demonstrated NGF/TrkA promoted the PC cell proliferation and invasion in the co-culture system by the activation of the PI3K/AKT/GSK signal cascade, providing a potential therapeutic target for PC patients.

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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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