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Updated: Jun 20, 2026
Translationally-Relevant Tumor Resection Model for Murine Preclinical Models of Oral Squamous Cell Carcinoma
Published on: April 3, 2026
A mouse model for oral squamous cell carcinoma
Remilio A L Schoop1, Mathieu H M Noteborn, Robert J Baatenburg de Jong
1Department of Otolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands. r.a.l.schoop@lumc.nl
Abstract:
Despite recent advances, the prognosis of oral squamous cell carcinoma is still poor. Therapeutic options such as radiotherapy, chemotherapy, surgery and the novel treatment option gene therapy are being investigated in animal models. Diverse models have been studied to induce oral squamous cell carcinomas. The carcinogenic 4-nitroquinoline-1-oxide (4NQO) model has proven to be successful although until now it is unknown at what time point the established tumor is a representative squamous cell carcinoma and has a suitable volume for scientific treatment. For this end we applied 4NQO 3 times a week during 16 weeks and measured the volume of tumor tissue each week until the end of the experiment at 40 weeks. Concurrent histopathology at different time points up to the end of the experiment revealed that all mice bearing oral tumors were diagnosed with squamous cell carcinoma. Immunohistochemistry with markers cyclin D1 and E-cadherin revealed that the generated mouse oral tumors showed strong similarities with the described immunopathology in human oral tumors. The 4NQO model is a suitable alternative for preclinical gene therapy experiments with primary oral tumors. Future survey of therapeutic options in the carcinogenic 4NQO model should be conducted around 40 weeks after the start of the treatment.
Insights
The 4-nitroquinoline-1-oxide (4NQO) model effectively induces oral squamous cell carcinoma in mice. Tumors are suitable for preclinical research around 40 weeks, showing similarities to human oral tumors.
Area of Science:
- Oncology
- Preclinical Cancer Research
- Animal Models
Background:
- Oral squamous cell carcinoma (OSCC) has a poor prognosis despite advances in treatment.
- Effective and reliable animal models are crucial for investigating novel OSCC therapies, including gene therapy.
- The 4-nitroquinoline-1-oxide (4NQO) model is widely used but lacks defined timelines for tumor development and suitability for research.
Purpose of the Study:
- To determine the optimal time point for utilizing 4NQO-induced oral tumors in preclinical research.
- To validate the 4NQO model's capacity to generate OSCCs representative of human disease.
- To assess the suitability of 4NQO-induced tumors for scientific treatment studies.
Main Methods:
- Mice were administered 4-nitroquinoline-1-oxide (4NQO) three times weekly for 16 weeks.
- Tumor volume was measured weekly for up to 40 weeks.
- Histopathology and immunohistochemistry (using cyclin D1 and E-cadherin markers) were performed at various time points.
Main Results:
- All mice developed oral tumors diagnosed as squamous cell carcinoma.
- Tumor development and progression were monitored over 40 weeks.
- Immunohistochemical analysis revealed similarities between mouse and human OSCC immunopathology.
Conclusions:
- The 4NQO model is a suitable and reproducible method for generating oral squamous cell carcinomas in mice.
- The optimal time for utilizing 4NQO-induced OSCCs in preclinical studies is approximately 40 weeks post-treatment initiation.
- This model serves as a valuable platform for evaluating therapeutic strategies, particularly gene therapy, for OSCC.
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