Establishment of a pancreatic cancer animal model using the pancreas-targeted hydrodynamic gene delivery method

Osamu Shibata; Kenya Kamimura; Yuto Tanaka; Kohei Ogawa; Takashi Owaki; Chiyumi Oda; Shinichi Morita; Atsushi Kimura; Hiroyuki Abe; Satoshi Ikarashi; Kazunao Hayashi; Takeshi Yokoo; Shuji Terai

Molecular Therapy: Nucleic Acids (Jun 2022)

Establishment of a pancreatic cancer animal model using the pancreas-targeted hydrodynamic gene delivery method

Osamu Shibata,
Kenya Kamimura,
Yuto Tanaka,
Kohei Ogawa,
Takashi Owaki,
Chiyumi Oda,
Shinichi Morita,
Atsushi Kimura,
Hiroyuki Abe,
Satoshi Ikarashi,
Kazunao Hayashi,
Takeshi Yokoo,
Shuji Terai

Affiliations

Osamu Shibata: 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
Kenya Kamimura: 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; Corresponding author. Kenya Kamimura, 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.
Yuto Tanaka: 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
Kohei Ogawa: 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
Takashi Owaki: 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
Chiyumi Oda: 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
Shinichi Morita: 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
Atsushi Kimura: 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
Hiroyuki Abe: 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
Satoshi Ikarashi: 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
Kazunao Hayashi: 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
Takeshi Yokoo: 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
Shuji Terai: 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

Journal volume & issue: Vol. 28
pp. 342 – 352

Abstract

Read online

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. KRASG12D-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 KRASG12D and YAP enhanced these effects. The repeat hydrodynamic gene delivery of KRASG12D + YAP 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. KRASG12D and YAP 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.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

About the journal

Abstract

Keywords