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Establishment of a DEN-induced mouse model of esophageal squamous cell carcinoma metastasis

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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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Authors and Affiliations

  1. Department of Frontier Surgery, School of Medicine, Chiba University, Graduate School of Medicine, Chiba, Japan

    Kazuo Narushima & Hisahiro Matsubara

  2. Department of Surgery, School of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan

    Hideaki Shimada

  3. Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan

    Shigeru Yamada

  4. Department of Radiation Effects Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Shizuko Kakinuma, Takamitsu Morioka & Yoshiya Shimada

Authors
  1. Kazuo Narushima
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  2. Hideaki Shimada
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  3. Hisahiro Matsubara
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  4. Shigeru Yamada
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  5. Shizuko Kakinuma
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  6. Takamitsu Morioka
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  7. Yoshiya Shimada
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Corresponding author

Correspondence to Hideaki Shimada.

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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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplemental Figure 1. Change in water intake volumes (JPG 78 kb)

Supplemental Figure 2. Median number of liver tumors and lung tumors (JPG 80 kb)

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)

Supplemental Figure 4. Outline of the experiment (PPT 76 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

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