Shibata Osamu, Kamimura Kenya, Tanaka Yuto, Ogawa Kohei, Owaki Takashi, Oda Chiyumi, Morita Shinichi, Kimura Atsushi, Abe Hiroyuki, Ikarashi Satoshi, Hayashi Kazunao, Yokoo Takeshi, Terai Shuji
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 1-757 Asahimachi-dori Chuo-ku, Niigata 951-8510, Japan.
Department of General Medicine, Niigata University School of Medicine, Niigata, 1-757 Asahimachi-dori Chuo-ku, Niigata 951-8510, Japan.
Mol Ther Nucleic Acids. 2022 Mar 28;28:342-352. doi: 10.1016/j.omtn.2022.03.019. eCollection 2022 Jun 14.
This research developed an easy-to-use, reproducible pancreatic cancer animal model utilizing pancreas-targeted hydrodynamic gene delivery to deliver human pancreatic cancer-related genes to the pancreas of wild-type rats. -induced pancreatic intraepithelial neoplasia lesions showed malignant transformation in the main pancreatic duct at 4 weeks and developed acinar-to-ductal metaplasia, which led to pancreatic ductal adenocarcinoma within 5 weeks, and the gene combination of and enhanced these effects. The repeat hydrodynamic gene delivery of + combination at 4 weeks showed acinar-to-ductal metaplasia in all rats and pancreatic ductal adenocarcinoma in 80% of rats 1 week later. Metastatic tumors in the liver, lymph nodes, and subcutaneous lesions and nervous invasion were confirmed. and combined transfer contributes to the E- to N-cadherin switch in pancreatic ductal adenocarcinoma cells and to tumor metastases. This pancreatic cancer model will speed up pancreatic cancer research for novel treatments and biomarkers for early diagnosis.
本研究利用胰腺靶向性流体动力学基因递送技术,开发了一种易于使用且可重复的胰腺癌动物模型,将人类胰腺癌相关基因递送至野生型大鼠的胰腺。诱导的胰腺上皮内瘤变病变在4周时主胰管出现恶性转化,并发展为腺泡-导管化生,5周内导致胰腺导管腺癌,且[具体基因1]和[具体基因2]的基因组合增强了这些效应。4周时重复进行[具体基因1]+[具体基因2]组合的流体动力学基因递送,所有大鼠均出现腺泡-导管化生,1周后80%的大鼠出现胰腺导管腺癌。证实有肝、淋巴结转移瘤以及皮下病变和神经侵犯。[具体基因1]和[具体基因2]联合转移促成胰腺导管腺癌细胞中E-钙黏蛋白向N-钙黏蛋白的转变以及肿瘤转移。这种胰腺癌模型将加速胰腺癌新型治疗方法和早期诊断生物标志物的研究。