Cell invasion, RAGE expression, and inflammation in oral squamous cell carcinoma (OSCC) cells exposed to e-cigarette flavoring

Clin Exp Dent Res. 2020 Dec;6(6):618-625. doi: 10.1002/cre2.314. Epub 2020 Aug 11.

Abstract

Objective: Electronic cigarettes have given rise to a new, largely unregulated market within the smoking industry. While generally supposed to be less harmful than traditional tobacco smoke, awareness of the biological effects of electronic cigarette liquid is still scarce. Our objective was to determine the impact of electronic cigarette flavoring and nicotine on gingival squamous cell carcinoma invasion, RAGE expression, and the elaboration of pro-inflammatory molecules.

Methods and materials: Gingival and tongue squamous cell carcinoma cells were exposed to Red Hot or Green Apple flavored electronic cigarette flavoring with or without nicotine. Immunofluorescence determined RAGE expression. Real-time cellular invasion was assessed using a RTCA DP instrument. Culture medium was assayed for cytokine secretion.

Results: Compared to controls we observed: increased cell invasion in gingival cells with Red Hot electronic cigarette flavoring and decreased cell invasion with Green Apple; decreased cell invasion in tongue cells treated with Red Hot electronic cigarette flavoring and no differences in invasion with Green Apple; flavor and nicotine dependent increases in RAGE expression; and differential expression of IL-1α, IL-8, and MMP-13.

Conclusion: We conclude that electronic cigarette flavoring and nicotine orchestrate differential regulation of oral squamous cell carcinoma (OSCC) cell invasion and inflammatory effects. This study provides an important initial step in dissecting RAGE-mediated mechanisms of cancerous invasion and molecular avenues employed by OSCC.

Keywords: RAGE; carcinoma; eCig; oral.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Electronic Nicotine Delivery Systems*
  • Flavoring Agents / adverse effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / pathology
  • Mouth Neoplasms / chemically induced*
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / pathology
  • Receptor for Advanced Glycation End Products / genetics*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • AGER protein, human
  • Flavoring Agents
  • Receptor for Advanced Glycation End Products