Abstract
Background
Syngeneic transplantation mouse models have been used to evaluate the efficacy of immunotherapy in addition to radiotherapy and chemotherapy for treating cancer. However, the mouse models of esophageal squamous cell carcinoma have yet to be established. Therefore, we aimed to develop a mouse model of esophageal squamous cell carcinoma.
Methods
Male and female Balb/c, C3H, and C57Bl mice received diethyl nitrosamine continuously for 4 months. On completion of the 200-day treatment period, animals were killed, and esophageal, forestomach, lung, and liver samples were examined macroscopically and by the histopathological analysis. Induced tumors from C3H female mice were mechanically dissociated into small pieces and were mixed with the brain homogenates, and injected into interscapular region subcutaneously into syngeneic C3H female mice to evaluate tumor growth and/or metastatic potential.
Results
The incidence of esophageal/forestomach squamous cell carcinoma varied according to mouse strain and gender, and the C3H mouse was found to be most susceptible. Pathologically, tumors were predominantly well-differentiated squamous cell carcinoma, with a proportion of tumors developing distant metastases. Transplanted esophageal squamous cell carcinoma cells developed subcutaneous tumors in syngeneic mice, with distant metastases into the lung. Metastatic tumors had poorly differentiated components histologically with Ki-67 and p53 expression. Metastatic tumors had lower p21 expression than transplanted tumors.
Conclusion
In the present study, we demonstrate the establishment of a mouse model esophageal squamous cell carcinoma allowing transplantation into syngeneic mice with distant metastatic potential. We believe that the present syngeneic mouse model will have utility in various preclinical research fields, including cancer immunotherapy.
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Abbreviations
- DEN:
-
Diethyl nitrosamine
- SCC:
-
Squamous cell carcinoma
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Acknowledgments
This work was partly supported by the Grant-in-Aid for Scientific Research (#24591961) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Ethical Statement
The present study protocol was approved by the Institutional Animal Care and Use Committee of the National Institute of Radiological Sciences (H18-1076).
Conflict of interest
All the authors have no conflict of interest on this project.
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10388_2016_555_MOESM3_ESM.jpg
Supplemental Figure 3. Microscopic appearance of lung and liver tumors. (a) Lung, well-differentiated adenocarcinoma. (b) Liver, well-differentiated hepatocellular carcinoma. (c) Liver, angiosarcoma (JPG 118 kb)
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Narushima, K., Shimada, H., Matsubara, H. et al. Establishment of a DEN-induced mouse model of esophageal squamous cell carcinoma metastasis. Esophagus 14, 131–137 (2017). https://doi.org/10.1007/s10388-016-0555-3
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DOI: https://doi.org/10.1007/s10388-016-0555-3