Annual Report 2023
Central Animal Division
Hidetoshi Kassai, Mami Takahashi, Mie Naruse, Yusuke Sakai, Yurika Shiotani, Daisuke Ito, Saori Kobayashi, Chihiro Nishizawa, Towa Nagai, Haruka Taniguchi, Shinichi Tamura, Hiyuu Seino
Introduction
In the Central Animal Division, we operate the animal facility and conduct the breeding and management of mice and rats in accordance with the rules established by the Animal Experiment Safety Management Committee and the Animal Experiment Facility Users Subcommittee. Additionally, in line with the regulations of the Animal Experiment Ethics Committee, we promote proper animal experiments with consideration for animal welfare. To support animal experimentation, we produce genetically modified mice through genome editing techniques and engage in technological development related to embryo engineering.
In cancer research, we analyze the genetic mutations and morphological changes associated with the passage of patient-derived xenograft (PDX) models, as well as changes in their characteristics related to the organoid formation. We also establish pancreatic cancer cell lines from PDX and mouse pancreatic cancer models, conduct characterization analyses, and provide these cell lines to researchers within and outside of the NCC for collaborative research.
Research Activities
Regarding the operation of the animal facility, we conduct daily breeding and management to ensure proper animal experimentation, and we strive to enhance animal welfare for users by holding animal experimentation workshops. Additionally, to insource the production of genetically modified mice, we have established a system for the rapid and efficient generation of genetically engineered animals using CRISPR/Cas9 to introduce mutations in mouse fertilized eggs.
We have cultured organoids derived from colorectal cancer patients and cancer-associated fibroblasts from the same cases, establishing a co-culture assessment system to evaluate interactions between stromal cells and cancer cells. We have also advanced the development of chemical carcinogenesis models using mouse normal epithelial organoids.
We established PDX models of endometrial cancer and compared genomic mutations and histological changes during passage with the original tumors. The results showed that endometrial cancers retained their histopathological characteristics, whereas the sarcomatous component predominated in sarcomatoid cancers.
In collaboration with external scientists, we have conducted research on the anti-cancer effects of natural components using PDX models of pancreatic and colorectal cancers, as well as studies aimed at establishing organoid lines from PDX strains derived from acinar cell carcinoma, a rare form of pancreatic cancer.
Education
We hold animal experimentation workshops aimed at conducting proper animal experiments and review animal experimentation proposals to ensure that appropriate practices based on animal welfare are implemented through education and hands-on training.
Future Prospects
The demand for animal experimentation at the Tsukiji campus is on the rise, and recent cancer research indicates the necessity of understanding cancer not just at the cellular level but as part of the whole organism system. Moving forward, we aim to promote research and support technical development to operate facilities that enable higher-quality animal experiments.
List of papers published in 2023
Journal
1. Ono R, Kuwagata M, Naruse M, Watanabe A, Takano M, Hasegawa T, Takashima H, Yoshioka Y, Ochiya T, Hirabayashi Y, Kitajima S. Extracellular vesicle small RNAs secreted from mouse amniotic fluid induced by repeated oral administration of VPA to pregnant mice. Fundamental Toxicological Sciences, 11:37-56, 2024
2. Terasaki M, Tsuruoka K, Tanaka T, Maeda H, Shibata M, Miyashita K, Kanemitsu Y, Sekine S, Takahashi M, Yagishita S, Hamada A. Fucoxanthin Inhibits Development of Sigmoid Colorectal Cancer in a PDX Model With Alterations of Growth, Adhesion, and Cell Cycle Signals. Cancer genomics & proteomics, 20:686-705, 2023
3. Imai T, Yoshida H, Machida Y, Kuramochi M, Ichikawa H, Kubo T, Takahashi M, Kato T. Alteration in molecular properties during establishment and passaging of endometrial carcinoma patient-derived xenografts. Scientific reports, 13:8511, 2023
4. Imai T, Naruse M, Machida Y, Fujii G, Mutoh M, Ochiai M, Takahashi M, Nakagama H. Feeding a High-Fat Diet for a Limited Duration Increases Cancer Incidence in a Breast Cancer Model. Nutrition and cancer, 75:713-725, 2023
5. Toyoda Y, Miyata H, Uchida N, Morimoto K, Shigesawa R, Kassai H, Nakao K, Tomioka NH, Matsuo H, Ichida K, Hosoyamada M, Aiba A, Suzuki H, Takada T. Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations. Pflugers Archiv, 475:489-504, 2023
6. Kodera T, Takeuchi RF, Takahashi S, Suzuki K, Kassai H, Aiba A, Shiozawa S, Okano H, Osakada F. Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids. Biochemical and biophysical research communications, 657:119-127, 2023
7. Ishino F, Itoh J, Irie M, Matsuzawa A, Naruse M, Suzuki T, Hiraoka Y, Kaneko-Ishino T. Retrovirus-Derived RTL9 Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain. International journal of molecular sciences, 24:14884, 2023
8. Terasaki M, Suzuki S, Tanaka T, Maeda H, Shibata M, Miyashita K, Kuramitsu Y, Hamada J, Ohta T, Yagishita S, Hamada A, Sakamoto Y, Hijioka S, Morizane C, Takahashi M. Anticancer Effects of Fucoxanthin in a PDX Model of Advanced Stage Pancreatic Cancer with Alteration of Several Multifunctional Molecules. Onco, 3:217-236, 2023