Development of a murine model of oral carcinogenesis: an accelerated tool for biomarker and anti-tumour drug discovery

Abstract

Oral squamous cell carcinoma (OSCC) is the most common cancer in Pakistani men and the second most common cancer in women. The objective of our study was to devise a novel accelerated murine model of oral carcinogenesis that can be exploited as a tool to investigate the cancer circuitry involved in OSCC and to identify molecules of diagnostic, therapeutic and prognostic significance. A total of 40 healthy male, 6–8 weeks old, 22 ± 2 gram, Naval Medical Research Institute (NMRI) outbred strain mice were recruited in the experiment. NMRI mice are commonly used for animal experiments in various fields of biology and for drug toxicity. Of these, 25 mice underwent the oral carcinogenesis regimen via topical application of 0.5% 9,10-dimethyl-1,2-benzanthracene (DMBA) on the lower left lip for a maximum of 20 weeks and 15 mice were used as controls (without the carcinogenic regimen). Exophytic tissue masses were harvested, fixed in 10% formalin and stained with haematoxylin and eosin (H&E) for microscopic diagnosis. Additionally, the expression levels of CK 5/6, p53 and Ki-67 were investigated using immunohistochemistry. Of the 25 mice which underwent the carcinogenic regimen, 21 developed moderately differentiated squamous cell carcinoma and 1 showed dysplastic features with foci of invasion. Three mice were found dead with lesion(s). CK 5/6 showed strong positivity (100%) and p53 and Ki-67 showed patchy (<30%) strong positivity in OSCC, suggesting the similarity of our model to human OSCC. We present an accelerated, close-to-human carcinogenesis, model of oral carcinogenesis using DMBA in NMRI mice that can be exploited to study the pathogenesis of oral squamous cell carcinoma and subsequently devise immunotherapy or targeted therapy.

Mouse Models for Head and Neck Squamous Cell Carcinoma

“…After 6 wk of DMBA-TPA treatment, papilloma with or without dysplasia and even SCC could be observed in the buccal mucosa, while 4NQO-treated mice developed SCCs in the tongue rather than buccal mucosa (Kim et al 2002). Syed et al (2022) developed SCC in the left lower lip by application of 0.5% DMBA alone. The average duration to develop lesion was 84.56 d, with an overall tumor burden of 4.64 lesions per mouse (Syed et al 2022).…”

“…Syed et al (2022) developed SCC in the left lower lip by application of 0.5% DMBA alone. The average duration to develop lesion was 84.56 d, with an overall tumor burden of 4.64 lesions per mouse (Syed et al 2022). Apart from serving as a platform model for carcinogen-induced SCC, numerous murine oral cancer cell lines have been derived from distinct tumors induced by DMBA.…”