Abstract

One of the major risk factors for head and neck squamous cell carcinoma (HNSCC) is tobacco smoke exposure, but the mechanisms that can account for disease development remain to be fully defined. Utilizing our HNSCC mouse model, we analyzed oral squamous cell carcinomas (OSCC) induced by the active metabolite of a common smoke constituent, dibenzo[a,l]pyrene diol-epoxide (DBPDE). Analyzing protein expression by either immunofluorescence or immunohistochemistry, we identified biologic processes that are dysregulated in premalignant and invasive cancer lesions induced by DBPDE. Interestingly, p120ctn expression is downregulated in both stages of the disease. In addition to decreased p120ctn expression, there was also increased proliferation (as measured by Ki67), inflammation (as measured by NFkB (p65) expression), neovascularization (as measured by CD31) and recruitment of Ly6G-positive immune cells as well as strong EGFR expression. We also examined the effect of the chemopreventive agent black raspberry (BRB) on p120ctn and EGFR protein expression in DBPDE treated mice. p120ctn, but not EGFR, protein expression increased in mice treated with BRB. Our results suggest that modulation of p120ctn may, in part, account for the mechanism by which BRB inhibits DBPDE induced OSCC in mice.

Highlights

  • Head and neck squamous cell carcinoma (HNSCC), including oral cavity, oropharynx, nasopharynx, hypopharynx and larynx malignancies, accounted for 878,348 new cases and 444,347 deaths in 2020 [1]

  • Our results indicated that black raspberry (BRB) did not alter the levels of EGFR expression in oral tissues of mice treated with DBPDE

  • We have demonstrated that DBPDE induces many changes in the epithelium of the oral cavity as well as in its tissue microenvironment (Fig 7)

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Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC), including oral cavity, oropharynx, nasopharynx, hypopharynx and larynx malignancies, accounted for 878,348 new cases and 444,347 deaths in 2020 [1]. Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the most common HNSCC types resulting in an estimated. Black raspberry restores p120ctn in DBPDE-induced oral tumors no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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