The Impact of Electronic Cigarette Vapor and Cigarette Smoke on Oral Squamous Cell Carcinoma Invasion and Inflammation

Objectives: Oral squamous cell carcinoma (OSCC) is a malignancy affecting approximately 30,000 people annually in the United States, and it has been strongly associated with tobacco exposure. While the adverse effects of cigarette smoke on OSCC are well established, the health impacts of electronic cigarettes (eCig), which deliver aerosolized flavors with or without nicotine, remain unclear. Our study aimed to compare the effects of eCig vapor extract (EVE) and cigarette smoke extract (SHS) on OSCC cell invasion, as well as the associated inflammatory responses.
Methods: Gingival-derived Ca9-22 cells were exposed to eCig vapor extracts from Red Hot or Green Apple flavors, with or without nicotine, for 6 hours. Separately, Ca9-22 cells were treated with cigarette smoke extract and semi-synthetic glycosaminoglycan ethers (SAGEs), a modulator of the receptor for advanced glycation end-products (RAGE), which is upregulated by second-hand smoke. Cellular invasion was measured in real-time, and protein expression was assessed using western blot analysis.
Results: We observed that both eCig vapor and cigarette smoke extracts increased OSCC cell invasion, although the molecular mechanisms differed. EVE exposure led to increased expression of NF-kB, TNF-α, ERK, JNK, and matrix metalloproteinase (MMP)-13, particularly in cells treated with Apple EVE. Cigarette smoke extract increased RAGE expression, along with Ras, AKT, and NF-kB activation, and enhanced expression of MMPs 2, 9, and 14. Notably, SAGEs were effective in inhibiting RAGE-dependent OSCC cell invasion induced by cigarette smoke extract.
Conclusions: In conclusion, both eCig vapor and cigarette smoke contribute to OSCC cell invasion via distinct but overlapping inflammatory and molecular pathways. These findings highlight the need for further research to fully elucidate the health risks associated with newer tobacco alternatives, such as eCig, in relation to traditional cigarette smoke exposure.