Li Yaxiong, Zhang Yongping, Liu Jiansheng
Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People's Republic of China.
Cancer Manag Res. 2019 Jun 6;11:5147-5156. doi: 10.2147/CMAR.S204260. eCollection 2019.
The biological functions of neuropilin and tolloid-like 2 () in the progression of pancreatic cancer remained unexplored. We aimed to investigate the biological roles and underlying molecular mechanisms of in pancreatic cancer. Thirty paired pancreatic tumor tissue samples and corresponding nontumor tissues were obtained from 30 pancreatic cancer patients who did not receive preoperative chemotherapy or radiotherapy. The changes in multiple cellular functions associated with tumor progression were assessed after knockdown/overexpression in pancreatic cancer cell lines. Additionally, a mouse-xenograft model was developed to verify the in vitro results. was upregulated in pancreatic tumor tissues. Elevated expression of was not only associated with an advanced tumor stage, but was also a prediction of poor prognosis for pancreatic cancer patients. Knockdown of in pancreatic cancer cell lines arrested the cell cycle and inhibited cell proliferation, colony formation, invasion, and migration; in contrast, overexpression of had an opposite effect on all of these parameters. A specific inhibitor, cryptotanshinone, reversed the tumor-promoting effects induced by overexpression in pancreatic cancer. Western blot analysis showed that invasion and migration were closely related to epithelial-mesenchymal transition, and that the signaling pathway was involved in -mediated oncogenic transformation in pancreatic cancer cells. Furthermore, knockdown significantly inhibited the growth of pancreatic tumor xenografts in nude mice. has an important role in the progression and metastasis of pancreatic cancer and could serve as a novel candidate for targeted therapy of pancreatic cancer.
在胰腺癌进展过程中，神经纤毛蛋白和类原肠胚样蛋白2（）的生物学功能仍未得到探索。我们旨在研究在胰腺癌中的生物学作用及其潜在的分子机制。从30例未接受术前化疗或放疗的胰腺癌患者中获取了30对胰腺肿瘤组织样本及相应的非肿瘤组织。在胰腺癌细胞系中敲低/过表达后，评估了与肿瘤进展相关的多种细胞功能的变化。此外，建立了小鼠异种移植模型以验证体外实验结果。在胰腺肿瘤组织中上调。的高表达不仅与肿瘤晚期相关，也是胰腺癌患者预后不良的一个预测指标。在胰腺癌细胞系中敲低可使细胞周期停滞，并抑制细胞增殖、集落形成、侵袭和迁移；相反，过表达对所有这些参数都有相反的作用。一种特异性抑制剂隐丹参酮可逆转过表达在胰腺癌中诱导的促肿瘤作用。蛋白质印迹分析表明，侵袭和迁移与上皮-间质转化密切相关，并且信号通路参与了介导的胰腺癌细胞致癌转化。此外，敲低显著抑制了裸鼠胰腺肿瘤异种移植瘤的生长。在胰腺癌的进展和转移中起重要作用，可作为胰腺癌靶向治疗的新候选靶点。
