Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, China.
J Cell Mol Med. 2020 May;24(10):5901-5910. doi: 10.1111/jcmm.15265. Epub 2020 Apr 15.
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.
胰腺癌(PC)是一种致死率持续居高不下的疾病,肿瘤微环境在 PC 进展过程中起着关键作用。在此,我们重点关注在胰腺星状细胞-胰腺癌细胞(PSCs-PC 细胞)共培养系统中,神经生长因子(NGF)/原肌球蛋白相关激酶 A(TrkA)如何影响 PC 的增殖和侵袭。采用 Transwell 作为共培养系统,以无接触方式直接共培养 PC 细胞和 PSCs,建立 PC 细胞和 PSCs 的模型。通过实时 PCR、免疫荧光、Western blot 分析或 ELISA 检测培养系统中 NGF 和 TrkA 的表达。采用小干扰 RNA 转染技术调节 PC 细胞中 TrkA 的表达。采用 Matrigel Transwell 检测法研究癌症侵袭的促进作用。在我们的研究中,NGF/TrkA 在 PSCs-PC 细胞共培养系统中过度表达,促进了 PC 细胞的侵袭和增殖。并且上皮-间充质转化相关基因受 si-TrkA 影响。此外,NGF/TrkA 通过激活 PI3K/AKT/GSK 信号通路调节 PC 细胞的增殖和侵袭。本研究表明,NGF/TrkA 通过激活 PI3K/AKT/GSK 信号级联促进共培养系统中 PC 细胞的增殖和侵袭,为 PC 患者提供了一个潜在的治疗靶点。