Histamine H4 receptor signalling in tongue cancer and its potential role in oral carcinogenesis - a short report

Abstract

Purpose: Recent reports indicate that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a role in carcinogenesis, and thus H4R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H4R in oral epithelial dysplasia (OED), and oral tongue squamous cell carcinomas (OTSCC) are unknown. The purpose of this study was to assess H4R expression in OTSCC patients and in cancer cell lines. Methods: Biopsies taken from OED, OTSCC, and healthy oral mucosa were studied by immunostaining. Primary human oral keratinocytes (HOKs) and two cancer cell lines (HSC-3 and SCC-25) were used for the in vitro studies. Quantitative real-time polymerase chain reaction was used to measure oncogene expression in the stimulated HOKs. Results: H4R-immunoreactivity was significantly reduced in OED and OTSCC samples, especially in the samples that had higher histopathological grades, which were also associated with noticeably increased mast cell counts. The presence of H4R in HSC-3 cells had clearly waned, in contrast to the HOKs. Gene expression data indicated that histamine-relevant inflammatory and environmental elements may participate in the regulation of some studied oncogenes. Conclusions: The results suggest a possible association between H4R and oral carcinogenesis. Furthermore, our findings raise a potential implication of histamine-mediated factors in the regulation of oncogenes, possibly via mast cells, as crucial components of tumor microenvironment. The identification of new elements that govern oral cancer development is highly important for the development of novel therapeutic approaches in OTSCC.