Three-dimensional xenograft model of dysplastic human laryngeal mucosa.

ABSTRACT

OBJECTIVE: Development of new therapeutic interventions in head and neck squamous cell carcinoma (HNSCC) will be facilitated by a model system that incorporates the ease of manipulation found in current tissue culture systems while retaining the three dimensional architecture that defines these malignancies. STUDY DESIGN: Original scientific investigation. METHODS: We describe a modification of a normal respiratory mucosa model system which recreates premalignant mucosal histology. Grossly normal appearing human mucosa is harvested from laryngectomy specimens, the mucosal epithelium selectively removed by protease treatment and placed in conventional tissue culture. After 7 days, the cells are seeded into denuded rat tracheas, which are in turn implanted in flank pockets of athymic nu/nu mice. The tracheas are incubated for three weeks, removed and the mucosa examined histologically. RESULTS: As originally described, normal pseudostratified squamous epithelium can be re-established in this system. Using human dysplastic mucosa as a starting material, mucosal histologies of respiratory dysplasia, squamous metaplasia, squamous dysplasia and squamous carcinoma in situ can be established. CONCLUSION: This system will provide a paradigm for future therapeutic interventions to modify the progression of squamous metaplasia to dysplasia, carcinoma in situ and invasive squamous cell carcinoma.