胰腺星状细胞通过HGF/c-Met通路促进胰腺癌周围神经侵袭
胰腺癌(PC)是一种高度致死性的癌症,具有强大的侵袭和转移能力,预后差,并且由于早期诊断和早期转移而导致顽固的高死亡率。因此,更好地了解转移的机制应为治疗目的提供新的机会。作为PC转移的一种途径,神经浸润(PNI)经常发生。然而,对PNI的分子机制仍知之甚少。在这项研究中,我们表明,肝细胞生长因子(HGF)/ c-Met途径在PC的PNI中起着至关重要的作用。我们发现,HGF通过激活HGF / c-Met途径促进PC细胞迁移和侵袭,并在体外增强神经生长因子(NGF)和基质金属蛋白酶9(MMP9)的表达。此外,在PC细胞和DRG的共培养模型中,HGF显着增加了PC细胞对背根神经节(DRG)的侵袭,并促进了DRG的生长。相反,当HGF / c-Met途径被siRNA阻断时,PC细胞的侵袭能力和PNI现象降低。总之,PSC通过HGF / c-Met途径促进PC细胞PNI。靶向HGF / c-Met信号通路可能是PC的有前途的治疗策略。**
Pancreatic Stellate Cells Facilitate Perineural Invasion of Pancreatic Cancer via HGF/c-Met Pathway
Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to late diagnosis and early metastasis. Therefore, a better understanding of the mechanisms of metastasis should provide novel opportunities for therapeutic purposes. As a route of metastasis in PC, perineural invasion (PNI) occurs frequently; however, the molecular mechanism of PNI is still poorly understood. In this study, we show that the hepatocyte growth factor (HGF)/c-Met pathway plays a vital role in the PNI of PC. We found that HGF promotes PC cell migration and invasion by activating the HGF/c-Met pathway, and enhances the expression of nerve growth factor (NGF) and matrix metalloproteinase-9 (MMP9) in vitro. Furthermore, HGF significantly increased PC cell invasion of the dorsal root ganglia (DRG) and promoted the outgrowth of DRG in cocultured models of PC cells and DRG. In contrast, the capacity for invasion and the phenomenon of PNI in PC cells were reduced when the HGF/c-Met pathway was blocked by siRNA. In conclusion, PSCs facilitate PC cell PNI via the HGF/c-Met pathway. Targeting the HGF/c-Met signaling pathway could be a promising therapeutic strategy for PC.
pmid: 31161784 Cell Transplant 影响因子: 3.477 发表日期: 20190604 官网 免费下载
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