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Establishment of a Pancreatic Cancer Animal Model Using the Pancreas-Targeted Hydrodynamic Gene Delivery Method

Apr 20 2022

Speed up the pancreatic cancer research: Development of the novel pancreatic cancer animal model

Pancreatic cancer has a significantly poor prognosis; therefore, the development of effective treatments is an unmet clinical need. The major drawback in this field was the lack of useful model animals, which delayed the establishment of markers for early diagnosis and therapeutic options. The research group of Professor KAMIMURA Kenya (Department of General Medicine, Niigata University School of Medicine in the Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University), SHIBATA Osamu (graduate student) and Professor TERAI Shuji in the same division established an effective carcinogenesis method with wild-type rats by selectively introducing oncogenes into the pancreas, using the pancreas-targeted hydrodynamic gene delivery method1 that has been developed by the group.

Research Results

  • Pancreatic cancer has a poor prognosis, and therefore, stablishing a animal model for developing effective treatments is an unmet need.
  • We have established a novel pancreatic carcinogenesis model in wild-type rats by the pancreas-targeted hydrodynamic gene delivery method developed by our research group.
  • We transferred the human pancreatic cancer-related gene of KRASG12D gene2 intravenously and developed pancreatic cancer in wild type rats with a tissue structure similar to that of human pancreatic cancer.
  • By combining oncogenes such as the KRASG12D gene and the YAP gene3, carcinogenesis in the pancreas was induced within five weeks after gene transfer.
  • The model animal showed liver metastasis, subcutaneous metastasis,  and lymph nodes metastasis, and invasion into nerves and surrounding organs mimicking the course of human pancreatic cancer.


Fig. Establishment of a Pancreatic Cancer Animal Model Using the Pancreas-Targeted Hydrodynamic Gene Delivery Method

[Glossary]

1. Hydrodynamic gene delivery method
This method introduces a gene from a blood vessel of a target organ using physical force (water pressure) to express the target protein in the organ cells. Authors have reported the usefulness of this method for gene therapy for the liver cirrhosis etc., and developed organ-selective gene transfer methods such as for the liver and pancreas. and verified the procedure in large animals for clinical application (Kamimura K, et al. Mol Ther, 2009; Kamimura K, et al. Mol Ther, 2010; Yokoo T & Kamimura K, et al. Gene Ther, 2013; Kamimura K, et al. Mol Ther Nucleic Acids, 2013; Abe H & Kamimura K, et al. Mol Ther Nucleic Acids, 2016; Kobayashi Y & Kamimura K, et al. Mol Ther Nucleic Acids, 2016; Ogawa K & Kamimura K, et al. Mol Ther Nucleic Acids, 2017)

2. KRAS gene
A member of the ras family of oncogenes, which transmits cell proliferation signals to the cell nucleus and promotes cell proliferation. Mutations in this gene (e.g. KRASG12D) play an important role in promoting carcinogenesis.

3. YAP gene
The YAP (yes-associated protein) gene is one oncogene that functions in various human cancers. Involved in cell proliferation as a transcription factor, the YAP is also reported to be inhibited by the Hippo signaling pathway, which enables controlling organ size and suppressing tumors.

Publication Details

Journal: Molecular Therapy - Nucleic Acids
Title: Establishment of a Pancreatic Cancer Animal Model using the Pancreas-Targeted Hydrodynamic Gene Delivery Method
Authors: 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
DOI: 10.1016/j.omtn.2022.03.019

News release

The article was released in EurekAlert, the online publication of the American Association for the Advancement of Science.

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